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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 1  |  Issue : 1  |  Page : 9-15

Ursolic acid and quercetin: Promising anticancer phytochemicals with antimetastatic and antiangiogenic potential


1 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab, India
2 Department of Biotechnology, M.M. University, Mulana, Ambala, Haryana, India
3 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab, India
4 University Institute of Engineering and Technology, Panjab University, Chandigarh, India

Date of Web Publication30-Jan-2018

Correspondence Address:
Dr. Hardeep Singh Tuli
Department of Biotechnology, M.M. University, Mulana, Ambala, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tme.tme_3_17

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  Abstract 


Despite available treatments, the incidence of the cancer is increasing and known to be a major cause of mortality worldwide. Plant-derived terpenoids and flavonoids are considered as promising therapeutic molecules, possessing a range of medicinal properties. These phytochemicals have been used as therapeutic agents for the treatment of the various chronic infections. Terpenoids and flavonoids, particularly ursolic acid (UA) and quercetin (Quer), respectively, are emerging as effective antitumor molecules with minimal cytotoxic effects on the normal body tissues. The regulatory role of these molecules in apoptosis, angiogenesis, invasion, or metastasis has been well documented in earlier studies. Angiogenesis and metastasis are the two important hallmarks for the survival of tumor and are responsible for 50% mortality in the cancer patients. Tumor angiogenesis and metastasis have been found to be significantly inhibited in the presence of UA and Quer. Evidence suggested that these phytochemicals inhibit the initiator and progressive cytokines, chemokines, and growth factors such as matrix metalloproteinases involved in extracellular matrix remodeling during tumor metastasis. In addition, the angiogenesis-associated factors such as hypoxia-inducible factor-α and vascular endothelial growth factor/vascular endothelial growth factor receptor have also been downregulated by UA and Quer. In the present review, molecular targets of UA and Quer, in tumor metastasis and angiogenesis, have been summarized.

Keywords: Antiangiogenesis, antimetastasis, cancer, flavonoids, quercetin, terpenoids, ursolic acid


How to cite this article:
Kashyap D, Tuli HS, Garg VK, Bhatnagar S, Sharma AK. Ursolic acid and quercetin: Promising anticancer phytochemicals with antimetastatic and antiangiogenic potential. Tumor Microenviron 2018;1:9-15

How to cite this URL:
Kashyap D, Tuli HS, Garg VK, Bhatnagar S, Sharma AK. Ursolic acid and quercetin: Promising anticancer phytochemicals with antimetastatic and antiangiogenic potential. Tumor Microenviron [serial online] 2018 [cited 2021 Nov 28];1:9-15. Available from: http://www.TMEResearch.org/text.asp?2018/1/1/9/207484




  Introduction Top


Metastasis and angiogenesis, the two important hallmarks of tumor that are responsible for more than 50% mortality.[1] In the tumor microenvironment (TME), signals are generated by the tumor cells, stromal cells, and immune cells so as to induce tumor invasion or metastasis and angiogenesis.[2] Metastasis is a crucial nature of vigorously growing cancer which spreads the cancer cells to the distant sites. Growing cancer requires continues food supply provided by new vessel formation, extension from the preexisting blood vessel into the tumor mass, and by the formation of tube-like structure by tumor cells itself to maintain aggressive proliferation.[3] Stromal cells are identified to play a vital role in tumor migration by secreting various growth signals (Epidermal growth factor (EGF), fibroblast growth factor [FGF], hepatocyte growth factor (HGF), transforming growth factor-β [TGF-β], and vascular endothelial growth factor [VEGF]) and cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).[4] Immune cells such as mast cells and macrophages, present in the TME, secret various cell surface molecules that stimulate the tumor cells for the invasion or metastasis. In addition, macrophages and mast cells are also known to stimulate endothelial cells for blood vessel formation.[5]

The mechanistic insight of metastasis process has revealed that matrix metalloproteases (MMPs) are mainly responsible for the degradation of extracellular matrix (ECM) and basement membrane during cancer progression and facilitate in the migration of cancer cells.[6] Whereas hypoxia-inducible factor-α (HIF-α), a central molecule in the angiogenesis, expresses under low nutrient and oxygen conditions and initiates the angiogenesis through VEGFs binding with the VEGF receptors (VEGFRs).[7] Since these are central molecules in the cancer growth; therefore, they may be used as prognostic or predictive markers and could be targeted to develop as an effective anticancer therapy.[8] Although a range of targeted therapies have been developed against these molecular markers to halt the cancer growth, due to laps in detailed mechanistic insight of tumor development and progression, their full effectiveness remains a challenge.

A variety of phytochemicals with promising antitumor potential has been tested against the various human cancer as well as associated malignancies.[9],[10],[11],[12],[13],[14],[15] Among these, ursolic acid (UA) and Quercetin (Quer), possessing widespread pharmacological importance, especially studied more intensively for anticancer properties.[16],[17],[18] UA, also called 3β-hydroxy-urs-12-en-28-oic-acid, is a pentacyclic triterpenoid [Figure 1]a, which has been reported from numerous classes of medicinal plants, such as Ligustrum lucidum, Glechoma riobotrya japonica, Rosmarinus offıcinalis, Hedyotis diffusa, hederacea, Vaccinium macrocarpon, Rhododendron hymenanthes Makino, Arctostaphylos uva-ursi Calluna vulgaris, Ocimum sanctum, and Eugenia jambolana and also present in wax coating of many fruits including apples, prunes, and pears.[19] Whereas, Quer (3, 5, 7, 3',4'-Pentahydroxyflavone) is a flavonol belonging to the class of polyphenolic flavonoids which is characterized by the presence of five hydroxyl groups on C6-C3-C6 backbone structure, especially a 3-OH group on the pyrone ring [Figure 1]b.[20] These phytochemicals have multiple targets in the cancer cell for inhibition of the tumor growth. The present review highlights the recent trends and advancements in antimetastasis and antiangiogenic mechanisms of action of UA and Quer [Figure 1].
Figure 1: Physical properties and chemical structures of ursolic acid (a) and quercetin (b)

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  Inhibition of Matrix Metalloproteinases Top


Studies over more than 40 years yielded enough evidence that are supporting the involvement of TME in the cancer survival and progression.[21] Stromal cell present in TME secretes MMPs which belong to the diverse family of endopeptidases that are capable of degrading various components of ECM.[22] MMPs and urokinase regulate the four important hall markers of cancer invasion such migration, invasion, metastasis, and angiogenesis by dissociates cell–cell and cell–ECM interaction and facilitates the tumor cell migration.[23] These zinc-dependent endopeptidases have been considered as potential prognostic and diagnostic marker in many types of human cancers and are being utilized as therapeutic targets in cancer treatment for the past 20 years.[6],[24],[25],[26] MMPs modulate the availability and function of several growth factors and their receptors such as insulin-like growth factors (IGFs) and epidermal growth factor receptor (EGFR) ligands.[27],[28],[29],[30] They also act as an antiapoptotic agent by cleaving Fas ligand death receptor through activating serine/threonine kinase Akt/protein kinase B signaling cascades using EGFR and IGFR pathways.[31],[32] UA and Quer, both phytochemicals have shown the inhibitory actions of these tumor supporting enzymes. For example, the cytokines such as IL-1β and TNF-α dependent expression of MMPs have been reduced after UA treatment in C6 glioma cells through the inactivation of NF-kβ-dependent signaling pathway.[33] Similarly, in the presence of UA, human breast cancer cells resulted in inactivation of NF-kβ and shown the downregulation MMP-2, u-PA, and upregulation of plasminogen activator inhibitor-1 through dephosphorylation of JNK, Akt, and mTOR.[34] The MAPK/P38, a class of MAPKs which stimulates overexpression of MMPs in cancer, has been suppressed by UA treatment found in a study on SNU-484 (Seoul National University-484) human gastric cancer cells.[35]

Further, a similar pattern of MMP-2 and MMP-9 activity was observed in different cancer cell lines in the presence of Quer, such as, an alimental supplement Flavin 7® having Quer and other bioactive as ingredients has been determined as an inhibitor of MMP-9 enzyme and capillary tube formation in in vitro studies done on human leukemia Jurkat cells and HeLa cells.[36] In melanoma, Quer inhibited STAT3 signaling and subsequently downregulated their target genes like MMP-2, MMP-9, Mcl-1, and VEGF importantly responsible for cell proliferation, invasion, or metastasis.[37] Lai et al. in 2013, during the study on oral cancer cells using Quer as an anticancer agent noted downregulation of PKC and RhoA which was further confirmed by the inhibition of MAPK, PI3K/AKT, NF-kβ, and uPA signaling pathways.[38]

In a similar way, UA also regulates the others substance that are associated with the initiation and progression of cancer.[16] The activity of proteases such as urokinase and cathepsin B correlated with cancer invasion and metastasis have been significantly inhibited after UA treatment.[39] Shanmugam et al. presented a study on TRAMP mice revealed that UA inhibits the cancer growth by suppressing proinflammatory cytokines and CXCR4/CXCL12 axis-dependent signaling pathways.[40] Furthermore, the same anticancer effect of UA was reported in H3255, A549, and Calu-6 cell lines which occurred through the inhibition of TGF-β1, Na(+)–K(+)-ATPase, and ICAM-1 expression.[41] Similarly, the inactivation of proteins that are associated with the adhesion and migration of tumor cells was reported in UA treated SW620 (human colonic adenocarcinoma cell line), B16-F10 (mouse melanoma cell line), and HepG2 cancer cell lines. Furthermore, using metastatic melanoma lung cancer C57BL/6 mice model, UA was sought as a promising antimetastatic drug.[42] Clearly, UA has the potential to suppress cancer metastasis to distant sites by regulating several cancer-associated mechanisms which provoke utilization of this molecule to inhibit the growth and increase patient's survival.


  Inhibition of Vascular Endothelial Growth Factor/vascular Endothelial Growth Factor Receptor Top


Blood vessel formation which requires VEGF and VEGFR is a crucial process for invasion and migration of solid malignancies.[43],[44],[45] VEGF receptor family has three tyrosine kinase members VEGFR-1, VEGFR-2, and VEGFR-3 also called Flt-1, KDR/Flk-1, and Flt-4, respectively, and these regulates the blood and lymphatic vessel formation.[46] VEGF/VEGFRs pathway is a key regulator of angiogenesis, usually expressed in endothelial cells during healthy physiology, which is also reported to be expressed during malignancy and associated with tumor growth, migration, and chemoresistance.[47],[48],[49],[50] VEGF-A which is secreted by both cancer and stromal cells preferentially binds to VEGFR-2 present on endothelial cells surface and then stimulates new vessel formation.[43] It is also found that VEGF can synergize with EGFR to promote autocrine signal-mediated tumor cell proliferation.[51] Therefore, VEGF/VEGFRs pathway may be considered as an important therapeutic marker to block the angiogenesis, and hence, the cancer proliferation.[52] UA and Quer in different experiments have been proven as the blocker of angiogenesis by targeting the VEGF and VEGFRs. The inhibitory effect of UA on H-ras, VEGF, and beta FGF (βFGF) was also described in a study using rat models.[53] Further, evidence also determined that Quer causes inhibition of HIF-1α, a protein known for production and secretion of VEGF which is essential for the angiogenesis.[54],[55],[56] Quer has also noticed as an antiangiogenic molecule in human umbilical vein and artery endothelial cells (HUVECs) and prostate cancer mouse model by inhibiting VEGF-R2-regulated AKT/mTOR/P70S6K signaling pathway.[57],[58] Studies on C57BL/6 and RF/6A mice models suggested that Quer attenuates VEGF-induced cancer proliferation and migration.[59],[60]

Similarly, the study on C57BL/6 mice model described that UA suppressed the expression of VEGF and inducible nitric oxide (iNO) that has associated with angiogenesis initiation.[61] Saraswati et al. analyzed that the UA acted as anticancer molecule by downregulating angiogenesis promoting factors such as VEGF, iNO synthase, TNF-α in Swiss Albino mice model with EAC tumor and significantly inhibited the cancer cell growth.[62] In addition, Lin et al. described that the antiangiogenic effect of UA in vivo as well as in vitro in HT-29 through downregulation of VEGF-A and βFGF which downstream control several cancer signaling pathways [Figure 2].[63]
Figure 2: High-metabolic rate during proliferation shifted aerobic metabolism toward anaerobic which lead to hypoxia in the tumor microenvironment. Hypoxia activates the hypoxia-inducible factor-α which subsequently activates the ligand of vascular endothelial growth factor receptor and stimulates the endothelia cells. Inducible nitric oxide synthase is another factor that could start angiogenesis pathway by activating the vascular endothelial growth factor. Similarly, activated matrix metalloproteases degrade the extracellular matrix for tumor cell migration. The presence of ursolic acid/quercetin modulates the multiple molecules in the cancer cell and hence stop the angiogenesis and metastasis (adopted from Kashyap et al. 2017)

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  Inhibition of Hypoxia-Inducible Factor-1α Top


Hypoxia or limited oxygen is a common condition in all solid malignancies where proliferating cells face deprived of oxygen and nutrients due to less blood supply.[64],[65] Under such environment, HIF-1α described as a key regulator of hypoxia-induced angiogenesis. Overexpressed HIF-1α regulates many substances that has associated with various aspects of the tumor, including angiogenesis, invasion and metastasis, cell survival, oxygen transport, iron metabolism, glycolysis, and glucose transport.[66],[67],[68],[69] It has found that it targets several genes including VEGFA, PIGF, VEGFR1, Tie-2, angiopoietin 1 and 2, MMPs, prolyl-4-hydroxylase, uPAR, FGF2, MCP-1, PDGF, SDF-1, and CXCR4, which has a significant role in angiogenesis.[7],[70],[71],[72],[73],[74] UA and Quer both phytochemicals with medicinal importance are considered as anticancer bioactive molecules in multiple studies. For example, a study utilizing Hep3B, Huh7, and HA22T cell lines, scientists claimed that UA suppresses the HIF-1α which then abolishes the expression of angiogenic factors such as VEGF and βFGF. Further, downregulation of HIF-1α could also be associated with the antioxidant effect of UA caused by reactive oxygen species (ROS) and NO species.[75] This flavonol molecule was found to inhibit several signaling pathways in malignancy associated with angiogenesis such as proliferation, cancer cell migration, and tube formation of endothelial cells.[76] Furthermore, the antiangiogenic effects of Quer were also proposed by chicken chorioallantoic membrane (CAM) assay.[77] Moreover, antitumor effect of Quer has associated with the reduced expression of endothelial NO synthase and arrest of mitotic microtubule polymerization in endothelial cells.[78],[79] Similarly, the antiangiogenic effect of Quer was also described in in vivo and in vitro studies on zebrafish embryos and HUVECs, respectively.[59] In addition, Quer also inhibited the ERK-signaling pathway determined in in vivo and in vitro studies.[59],[80],[81] This plant-derived molecule significantly suppressed TPA-induced activation of PKCd/ERK/AP-1-signaling in human breast cancer.[82] In MDA-MB-231 cells, an elevation in connexin 43 levels was noted after Quer treatment which ameliorated gap junctional intercellular communication, and hence, block the cancer proliferation and metastasis.[83] Thrombospondin-1, an endogenous antiangiogenic factor, was found to be upregulated in the presence of Quer which resulted in the suppression of prostate cancer PC-3 cell.[84] Quer also acted against the HGF/c-Met signaling pathway that has been proved by its inhibitory action on melanoma.[85] Since Quer inhibits multiple targets in angiogenesis and/or metastasis, it may be used as a potential anticancer drug molecule.

In addition, in vivo CAM assay revealed the potential role of UA in the inhibition of the newly forming vascularization system in the tumor mass.[86] Authors reported that UA treatment resulted in inhibition of STAT3, Akt/p70S6K, and sonic hedgehog signaling pathways which are already correlated with tumor survival, proliferation, invasion, and angiogenesis.[63] Clearly, UA has the potential to suppress tumor angiogenesis through numerous mechanisms, thereby this molecule could be considered as a potential tumor inhibiting agent in the years to come.


  Antioxidative Potential of Ursolic Acid and Quercetin Top


The microenvironment of the tumor is known to be affected by ROS generated during the high-rate metabolism. Further, these ROS have also been associated with the initiation and progression of other diseases such as neurodegeneration and cardiovascular.[87] Previous studies have shown that natural metabolites can be utilized as promising therapeutic agents to neutralize these ROS molecules. Proven in multiple studies, Nrf2 regulates the genes for antioxidant enzymes such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase contains replication elements (AREs). Various in vivo and in vitro models have shown that UA may not only overturned the reduced expression of these enzymes but may also significantly enhanced the survival rate.[88] Similarly, the hepatoprotective role of UA was observed against ethanol-induced oxidative effect in rat through modulating the expression levels of stress-associated molecular markers including ascorbic acid and tocopherol.[89] Furthermore, Quer has also been found to directly affect the ARE binding activity as well as gene expression of NQO1 in HepG2 cells.[90] In addition, Quer also known to stabilize Nrf2 protein by averting its degradation as well as by decrementing the expression levels of Keap1 repressor protein.[90] Similar effects of Quer have also been documented in various other cell lines such as colorectal adenocarcinoma (Caco-2 cells) and duodenum adenocarcinoma (HuTu 80) cells.[91]


  Drug Dosage and Toxicological Aspects of Ursolic Acid and Quercetin Top


Evidence has clearly suggested that UA and Quer might be utilized as valuable therapeutic agents for the treatment of the human cancers.[16],[18] However, drug dosage and toxicological studies of both molecules are further needed to be defined accurately. Besides, a number of positively published reports, few studies have reported the genotoxic effects of Quer.[92],[93] For example, at a concentration of 1133 mg/kg body weight/day in the male Wistar rats, Quer decreased the systolic blood pressure as well as cardiac hypertrophy along with increased in proteinuria.[94] In a 6-week study using Long-Evans Cinnamon rats, it was noted that 1% administration of Quer in the diet may lead to tubular necrosis.[95] On the other hand, toxicological study using UA has reported its LD50 concentration at 9.26 g/kg and nongenotoxic effects of UA extract.[96] Toxicological and pharmacokinetics studies of UAL (Ursolic acid liposomes) on 63 controls have revealed the manageable side effects with a tolerable dosage of 98 mg/m 2.[97]


  Conclusions and Future Perspectives Top


Evidence has supported that naturopathy significantly helps cure the difficult to treat diseases.[11],[98],[99] Being natural dietary molecules, UA and Quer possess lesser side effects as compared to cytotoxic drugs. These moieties also exhibit important anti-inflammatory and antioxidant effects by regulating the expression of Nrf-2 and NF-kβ. Since chronic inflammation has been significantly associated with initiation and progression of various human cancer types such as breast cancer, lung cancer, and colon cancer, the anti-inflammatory of these molecules further contributes to their anticancer role.[16],[100] Synergistically, in combination with natural or synthetic drugs, these bioactive molecules have been successfully shown to have the enhanced efficacy.[101] Therefore, the available information on antiangiogenic and antimetastatic role of UA and Quer may help the scientific community to design the novel therapeutic strategy which may increase the disease-free survival.In vitro studies and limited preclinical in vivo studies have suggested potential role of both UA and Quer in chemoprevention or cancer therapy, but lacking human data restricts their clinical use. A human study conducted to assess the potential role of Quer in ovarian cancer prevention concluded that dietary availability Quer did not decreased the risk of ovarian cancer.[102] In addition, it was shown that Quer exacerbated estrogen-induced breast tumors in rats.[103] Consequently, to increase the clinical utility of these phytochemicals, more data on human health control has to be required.

Acknowledgement

The authors fully acknowledge Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh for providing the requisite facility for the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bal A, Joshi K, Das A, Kashyap DB, Singh G. Significance of epithelial to mesenchymal transition (EMT) in breast cancer and implication on lymph node metastasis. Lab Invest 2015;95:34A.  Back to cited text no. 1
    
2.
Mbeunkui F, Johann DJ Jr. Cancer and the tumor microenvironment: A review of an essential relationship. Cancer Chemother Pharmacol 2009;63:571-82.  Back to cited text no. 2
[PUBMED]    
3.
Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002;29 6 Suppl 16:15-8.  Back to cited text no. 3
    
4.
Conklin MW, Keely PJ. Why the stroma matters in breast cancer: Insights into breast cancer patient outcomes through the examination of stromal biomarkers. Cell Adh Migr 2012;6:249-60.  Back to cited text no. 4
[PUBMED]    
5.
Irshad S, Grigoriadis A, Lawler K, Ng T, Tutt A. Profiling the immune stromal interface in breast cancer and its potential for clinical impact. Breast Care (Basel) 2012;7:273-80.  Back to cited text no. 5
[PUBMED]    
6.
Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002;2:161-74.  Back to cited text no. 6
[PUBMED]    
7.
Hirota K, Semenza GL. Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol 2006;59:15-26.  Back to cited text no. 7
[PUBMED]    
8.
Melillo G. Inhibiting hypoxia-inducible factor 1 for cancer therapy. Mol Cancer Res 2006;4:601-5.  Back to cited text no. 8
[PUBMED]    
9.
Tuli HS, Kashyap DB, Sharma AK, Kumar M, Sak K. Molecular targets of natural metabolites in cancer: Recent trends and advancements. J Biol Chem Sci 2016;3:208-15.  Back to cited text no. 9
    
10.
Tuli HS, Kashyap D, Sharma AK, Sandhu SS. Molecular aspects of melatonin (MLT)-mediated therapeutic effects. Life Sci 2015;135:147-57.  Back to cited text no. 10
[PUBMED]    
11.
Tuli HS, Kashyap DB, Sharma AK. Cordycepin: A cordyceps metabolite with promising therapeutic potential in fungal metab. Cham: Springer International Publishing; 2015. p. 1-22.  Back to cited text no. 11
    
12.
Tuli HS, Kumar G, Sandhu SS, Sharma AK, Kashyap D. Apoptotic effect of cordycepin on A549 human lung cancer cell line. Turk J Biol 2015;39:306-11.  Back to cited text no. 12
    
13.
Tuli HS, Sharma AK, Sandhu SS, Kashyap D. Cordycepin: A bioactive metabolite with therapeutic potential. Life Sci 2013;93:863-9.  Back to cited text no. 13
    
14.
Tuli HS, Sandhu SS, Kashyap DB, Sharma AK. Optimization of extraction conditions and antimicrobial potential of a bioactive metabolite, cordycepin from cordyceps militaris 3936. World J Pharm Pharm Sci 2014;3:1525-35.  Back to cited text no. 14
    
15.
Kashyap DB, Tuli HS, Sharma AK. Cordyceps ordycepsma Ahimalayan viagra with promising aphrodisiac potential. Austin Androl 2016;1:2015-6.  Back to cited text no. 15
    
16.
Kashyap D, Tuli HS, Sharma AK. Ursolic acid (UA): A metabolite with promising therapeutic potential. Life Sci 2016;146:201-13.  Back to cited text no. 16
[PUBMED]    
17.
Kashyap D, Sharma A, Tuli HS, Punia S, Sharma AK. Ursolic acid and oleanolic acid: Pentacyclic terpenoids with promising anti-inflammatory activities. Recent Pat Inflamm Allergy Drug Discov 2016;10:21-33.  Back to cited text no. 17
[PUBMED]    
18.
Kashyap DB, Sharma A, Mukherjee TK, Tuli HS. Quercetin and ursolic acid: Dietary moieties with promising role in tumor cell cycle arrest. Austin Oncol 2016;2:1010.  Back to cited text no. 18
    
19.
Li G, Zhang X, You J, Song C, Sun Z, Xia L, et al. Highly sensitive and selective pre-column derivatization high-performance liquid chromatography approach for rapid determination of triterpenes oleanolic and ursolic acids and application to Swertia species: Optimization of triterpenic acids extraction and pre-column derivatization using response surface methodology. Anal Chim Acta 2011;688:208-18.  Back to cited text no. 19
[PUBMED]    
20.
Marais JP, Deavours B, Dixon RA, Ferreira D. The stereochemistry of flavonoids. In: The Science of Flavonoids. New York: Springer; 2006. p. 1-46.  Back to cited text no. 20
    
21.
Bussard KM, Mutkus L, Stumpf K, Gomez-Manzano C, Marini FC. Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res 2016;18:84.  Back to cited text no. 21
    
22.
Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell 2010;141:52-67.  Back to cited text no. 22
[PUBMED]    
23.
Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 2011;278:16-27.  Back to cited text no. 23
[PUBMED]    
24.
Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 2006;69:562-73.  Back to cited text no. 24
[PUBMED]    
25.
Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 2009;27:5287-97.  Back to cited text no. 25
[PUBMED]    
26.
Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 1980;284:67-8.  Back to cited text no. 26
[PUBMED]    
27.
Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM. ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3. Biochem Biophys Res Commun 2000;278:511-5.  Back to cited text no. 27
[PUBMED]    
28.
Nakamura M, Miyamoto S, Maeda H, Ishii G, Hasebe T, Chiba T, et al. Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability. Biochem Biophys Res Commun 2005;333:1011-6.  Back to cited text no. 28
[PUBMED]    
29.
Gialeli CH, Kletsas D, Mavroudis D, Kalofonos HP, Tzanakakis GN, Karamanos NK. Targeting epidermal growth factor receptor in solid tumors: Critical evaluation of the biological importance of therapeutic monoclonal antibodies. Curr Med Chem 2009;16:3797-804.  Back to cited text no. 29
[PUBMED]    
30.
Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, et al. ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc Natl Acad Sci U S A 2005;102:9182-7.  Back to cited text no. 30
[PUBMED]    
31.
Kulik G, Klippel A, Weber MJ. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol Cell Biol 1997;17:1595-606.  Back to cited text no. 31
[PUBMED]    
32.
Sympson CJ, Talhouk RS, Alexander CM, Chin JR, Clift SM, Bissell MJ, et al. Targeted expression of stromelysin-1 in mammary gland provides evidence for a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression. J Cell Biol 1994;125:681-93.  Back to cited text no. 32
[PUBMED]    
33.
Huang HC, Huang CY, Lin-Shiau SY, Lin JK. Ursolic acid inhibits IL-1beta or TNF-alpha-induced C6 glioma invasion through suppressing the association ZIP/p62 with PKC-zeta and downregulating the MMP-9 expression. Mol Carcinog 2009;48:517-31.  Back to cited text no. 33
[PUBMED]    
34.
Yeh CT, Wu CH, Yen GC. Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol Nutr Food Res 2010;54:1285-95.  Back to cited text no. 34
[PUBMED]    
35.
Kim ES, Moon A. Ursolic acid inhibits the invasive phenotype of SNU-484 human gastric cancer cells. Oncol Lett 2015;9:897-902.  Back to cited text no. 35
[PUBMED]    
36.
Mojzis J, Varinska L, Mojzisova G, Kostova I, Mirossay L. Antiangiogenic effects of flavonoids and chalcones. Pharmacol Res 2008;57:259-65.  Back to cited text no. 36
[PUBMED]    
37.
Cao HH, Tse AK, Kwan HY, Yu H, Cheng CY, Su T, et al. Quercetin exerts anti-melanoma activities and inhibits STAT3 signaling. Biochem Pharmacol 2014;87:424-34.  Back to cited text no. 37
[PUBMED]    
38.
Lai WW, Hsu SC, Chueh FS, Chen YY, Yang JS, Lin JP, et al. Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Res 2013;33:1941-50.  Back to cited text no. 38
[PUBMED]    
39.
Jedinák A, Mucková M, Kost'álová D, Maliar T, Masterova I. Antiprotease and antimetastatic activity of ursolic acid isolated from Salvia officinalis. Z Naturforsch C 2006;61:777-82.  Back to cited text no. 39
    
40.
Shanmugam MK, Manu KA, Ong TH, Ramachandran L, Surana R, Bist P, et al. Inhibition of CXCR4/CXCL12 signaling axis by ursolic acid leads to suppression of metastasis in transgenic adenocarcinoma of mouse prostate model. Int J Cancer 2011;129:1552-63.  Back to cited text no. 40
[PUBMED]    
41.
Huang CY, Lin CY, Tsai CW, Yin MC. Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines. Toxicol In Vitro 2011;25:1274-80.  Back to cited text no. 41
[PUBMED]    
42.
Xiang L, Chi T, Tang Q, Yang X, Ou M, Chen X, et al. A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis. Oncotarget 2015;6:9295-312.  Back to cited text no. 42
[PUBMED]    
43.
Chung AS, Lee J, Ferrara N. Targeting the tumour vasculature: Insights from physiological angiogenesis. Nat Rev Cancer 2010;10:505-14.  Back to cited text no. 43
[PUBMED]    
44.
Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer 2013;13:871-82.  Back to cited text no. 44
[PUBMED]    
45.
Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005;69 Suppl 3:4-10.  Back to cited text no. 45
[PUBMED]    
46.
Rigiracciolo DC, Scarpelli A, Lappano R, Pisano A, Santolla MF, De Marco P, et al. Copper activates HIF-1a/GPER/VEGF signalling in cancer cells. Oncotarget 2015;6:34158-77.  Back to cited text no. 46
[PUBMED]    
47.
Guo S, Colbert LS, Fuller M, Zhang Y, Gonzalez-Perez RR. Vascular endothelial growth factor receptor-2 in breast cancer. Biochim Biophys Acta 2010;1806:108-21.  Back to cited text no. 47
[PUBMED]    
48.
Tanno S, Ohsaki Y, Nakanishi K, Toyoshima E, Kikuchi K. Human small cell lung cancer cells express functional VEGF receptors, VEGFR-2 and VEGFR-3. Lung Cancer 2004;46:11-9.  Back to cited text no. 48
[PUBMED]    
49.
Lee TH, Avraham HK, Jiang S, Avraham S. Vascular endothelial growth factor modulates the transendothelial migration of MDA-MB-231 breast cancer cells through regulation of brain microvascular endothelial cell permeability. J Biol Chem 2003;278:5277-84.  Back to cited text no. 49
[PUBMED]    
50.
Yang F, Tang X, Riquelme E, Behrens C, Nilsson MB, Giri U, et al. Increased VEGFR-2 gene copy is associated with chemoresistance and shorter survival in patients with non-small-cell lung carcinoma who receive adjuvant chemotherapy. Cancer Res 2011;71:5512-21.  Back to cited text no. 50
[PUBMED]    
51.
Lichtenberger BM, Tan PK, Niederleithner H, Ferrara N, Petzelbauer P, Sibilia M. Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 2010;140:268-79.  Back to cited text no. 51
[PUBMED]    
52.
Kieran MW, Kalluri R, Cho YJ. The VEGF pathway in cancer and disease: Responses, resistance, and the path forward. Cold Spring Harb Perspect Med 2012;2:a006593.  Back to cited text no. 52
[PUBMED]    
53.
Kim HY, Choi HR, Lee YJ, Cui HZ, Jin SN, Cho KW, et al. Accentuation of ursolic acid on muscarinic receptor-induced ANP secretion in beating rabbit atria. Life Sci 2014;94:145-50.  Back to cited text no. 53
[PUBMED]    
54.
Chen X, Dong XS, Gao HY, Jiang YF, Jin YL, Chang YY, et al. Suppression of HSP27 increases the anti-tumor effects of quercetin in human leukemia U937 cells. Mol Med Rep 2016;13:689-96.  Back to cited text no. 54
[PUBMED]    
55.
Lee KW, Kang NJ, Heo YS, Rogozin EA, Pugliese A, Hwang MK, et al. Raf and MEK protein kinases are direct molecular targets for the chemopreventive effect of quercetin, a major flavonol in red wine. Cancer Res 2008;68:946-55.  Back to cited text no. 55
[PUBMED]    
56.
Miao ZH, Feng JM, Ding J. Newly discovered angiogenesis inhibitors and their mechanisms of action. Acta Pharmacol Sin 2012;33:1103-11.  Back to cited text no. 56
[PUBMED]    
57.
Pratheeshkumar P, Budhraja A, Son YO, Wang X, Zhang Z, Ding S, et al. Quercetin inhibits angiogenesis mediated human prostate tumor growth by targeting VEGFR- 2 regulated AKT/mTOR/P70S6K signaling pathways. PLoS One 2012;7:e47516.  Back to cited text no. 57
[PUBMED]    
58.
Zhao D, Qin C, Fan X, Li Y, Gu B. Inhibitory effects of quercetin on angiogenesis in larval zebrafish and human umbilical vein endothelial cells. Eur J Pharmacol 2014;723:360-7.  Back to cited text no. 58
[PUBMED]    
59.
Li F, Bai Y, Zhao M, Huang L, Li S, Li X, et al. Quercetin inhibits vascular endothelial growth factor-induced choroidal and retinal angiogenesis in vitro. Ophthalmic Res 2015;53:109-16.  Back to cited text no. 59
[PUBMED]    
60.
Chen Y, Li F, Meng X, Li X. Suppression of retinal angiogenesis by quercetin in a rodent model of retinopathy of prematurity. Zhonghua Yi Xue Za Zhi 2015;95:1113-5.  Back to cited text no. 60
[PUBMED]    
61.
Kanjoormana M, Kuttan G. Antiangiogenic activity of ursolic acid. Integr Cancer Ther 2010;9:224-35.  Back to cited text no. 61
[PUBMED]    
62.
Saraswati S, Agrawal SS, Alhaider AA. Ursolic acid inhibits tumor angiogenesis and induces apoptosis through mitochondrial-dependent pathway in ehrlich ascites carcinoma tumor. Chem Biol Interact 2013;206:153-65.  Back to cited text no. 62
[PUBMED]    
63.
Lin J, Chen Y, Wei L, Hong Z, Sferra TJ, Peng J. Ursolic acid inhibits colorectal cancer angiogenesis through suppression of multiple signaling pathways. Int J Oncol 2013;43:1666-74.  Back to cited text no. 63
[PUBMED]    
64.
Poon E, Harris AL, Ashcroft M. Targeting the hypoxia-inducible factor (HIF) pathway in cancer. Expert Rev Mol Med 2009;11:e26.  Back to cited text no. 64
[PUBMED]    
65.
Ke Q, Costa M. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 2006;70:1469-80.  Back to cited text no. 65
[PUBMED]    
66.
Guillemin K, Krasnow MA. The hypoxic response: Huffing and HIFing. Cell 1997;89:9-12.  Back to cited text no. 66
[PUBMED]    
67.
Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3:721-32.  Back to cited text no. 67
[PUBMED]    
68.
Bos R, Zhong H, Hanrahan CF, Mommers EC, Semenza GL, Pinedo HM, et al. Levels of hypoxia-inducible factor-1 alpha during breast carcinogenesis. J Natl Cancer Inst 2001;93:309-14.  Back to cited text no. 68
[PUBMED]    
69.
Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, et al. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 1999;59:5830-5.  Back to cited text no. 69
[PUBMED]    
70.
Le QT, Giaccia AJ. HIF-alpha, a gender independent transcription factor. Clin Cancer Res 2003;9:2391-3.  Back to cited text no. 70
[PUBMED]    
71.
Silva P, Slevin NJ, Sloan P, Valentine H, Cresswell J, Ryder D, et al. Prognostic significance of tumor hypoxia inducible factor-1alpha expression for outcome after radiotherapy in oropharyngeal cancer. Int J Radiat Oncol Biol Phys 2008;72:1551-9.  Back to cited text no. 71
[PUBMED]    
72.
Tzao C, Lee SC, Tung HJ, Hsu HS, Hsu WH, Sun GH, et al. Expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF)-D as outcome predictors in resected esophageal squamous cell carcinoma. Dis Markers 2008;25:141-8.  Back to cited text no. 72
[PUBMED]    
73.
Uehara M, Sano K, Ikeda H, Nonaka M, Asahina I. Hypoxia-inducible factor 1 alpha in oral squamous cell carcinoma and its relation to prognosis. Oral Oncol 2009;45:241-6.  Back to cited text no. 73
[PUBMED]    
74.
Trastour C, Benizri E, Ettore F, Ramaioli A, Chamorey E, Pouysségur J, et al. HIF-1alpha and CA IX staining in invasive breast carcinomas: Prognosis and treatment outcome. Int J Cancer 2007;120:1451-8.  Back to cited text no. 74
    
75.
Lin CC, Huang CY, Mong MC, Chan CY, Yin MC. Antiangiogenic potential of three triterpenic acids in human liver cancer cells. J Agric Food Chem 2011;59:755-62.  Back to cited text no. 75
[PUBMED]    
76.
Kim DK, Baek JH, Kang CM, Yoo MA, Sung JW, Chung HY, et al. Apoptotic activity of ursolic acid may correlate with the inhibition of initiation of DNA replication. Int J Cancer 2000;87:629-36.  Back to cited text no. 76
[PUBMED]    
77.
Tan WF, Lin LP, Li MH, Zhang YX, Tong YG, Xiao D, et al. Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential. Eur J Pharmacol 2003;459:255-62.  Back to cited text no. 77
[PUBMED]    
78.
Jackson SJ, Venema RC. Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells. J Nutr 2006;136:1178-84.  Back to cited text no. 78
[PUBMED]    
79.
Sagar SM, Yance D, Wong RK. Natural health products that inhibit angiogenesis: A potential source for investigational new agents to treat cancer-Part 2. Curr Oncol 2006;13:99-107.  Back to cited text no. 79
[PUBMED]    
80.
Article O, Samavati SF, Mostafaie A. A highly pure sub-fraction of shallot extract with potent in vitro anti-angiogenic activity. Int J Mol Cell Med 2014;3:237-45.  Back to cited text no. 80
    
81.
Maniago KG, Mari CG, Pareja MC, Grace K, Maniago N. Angiogenic effect of Curcuma longa Linn. (turmeric) tea powder on the chorioallantoic membrane of 10-day old Annas luzonica (Duck) eggs. Ann Biol Res 2014;5:32-7.  Back to cited text no. 81
    
82.
Lin CW, Hou WC, Shen SC, Juan SH, Ko CH, Wang LM, et al. Quercetin inhibition of tumor invasion via suppressing PKC delta/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. Carcinogenesis 2008;29:1807-15.  Back to cited text no. 82
[PUBMED]    
83.
Conklin CM, Bechberger JF, MacFabe D, Guthrie N, Kurowska EM, Naus CC. Genistein and quercetin increase connexin43 and suppress growth of breast cancer cells. Carcinogenesis 2007;28:93-100.  Back to cited text no. 83
[PUBMED]    
84.
Yang F, Jiang X, Song L, Wang H, Mei Z, Xu Z, et al. Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo. Oncol Rep 2016;35:1602-10.  Back to cited text no. 84
[PUBMED]    
85.
Cao HH, Cheng CY, Su T, Fu XQ, Guo H, Li T, et al. Quercetin inhibits HGF/c-Met signaling and HGF-stimulated melanoma cell migration and invasion. Mol Cancer 2015;14:103.  Back to cited text no. 85
[PUBMED]    
86.
Cárdenas C, Quesada AR, Medina MA. Effects of ursolic acid on different steps of the angiogenic process. Biochem Biophys Res Commun 2004;320:402-8.  Back to cited text no. 86
    
87.
Tuli HS, Sandhu SS, Sharma AK. Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin. 3 Biotech 2014;4:1-12.  Back to cited text no. 87
    
88.
Martin-Aragón S, de las Heras B, Sanchez-Reus MI, Benedi J. Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes. Exp Toxicol Pathol 2001;53:199-206.  Back to cited text no. 88
    
89.
Saravanan R, Viswanathan P, Pugalendi KV. Protective effect of ursolic acid on ethanol-mediated experimental liver damage in rats. Life Sci 2006;78:713-8.  Back to cited text no. 89
[PUBMED]    
90.
Tanigawa S, Fujii M, Hou DX. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med 2007;42:1690-703.  Back to cited text no. 90
[PUBMED]    
91.
Odenthal J, van Heumen BW, Roelofs HM, te Morsche RH, Marian B, Nagengast FM, et al. The influence of curcumin, quercetin, and eicosapentaenoic acid on the expression of phase II detoxification enzymes in the intestinal cell lines HT-29, Caco-2, HuTu 80, and LT97. Nutr Cancer 2012;64:856-63.  Back to cited text no. 91
[PUBMED]    
92.
Ngomuo AJ, Jones RS. Genotoxicity studies of quercetin and shikimate in vivo in the bone marrow of mice and gastric mucosal cells of rats. Vet Hum Toxicol 1996;38:176-80.  Back to cited text no. 92
[PUBMED]    
93.
da Silva J, Herrmann SM, Heuser V, Peres W, Possa Marroni N, González-Gallego J, et al. Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test. Food Chem Toxicol 2002;40:941-7.  Back to cited text no. 93
    
94.
Kitamura Y, Nishikawa A, Nakamura H, Furukawa F, Imazawa T, Umemura T, et al. Effects of N-acetylcysteine, quercetin, and phytic acid on spontaneous hepatic and renal lesions in LEC rats. Toxicol Pathol 2005;33:584-92.  Back to cited text no. 94
[PUBMED]    
95.
Soares VC, Varanda EA, Raddi MS.In vitro basal and metabolism-mediated cytotoxicity of flavonoids. Food Chem Toxicol 2006;44:835-8.  Back to cited text no. 95
[PUBMED]    
96.
Jing-Bo LI. Acute and genetic toxicity of ursolic acid extract from Ledum pulastre L. Food Sci 2009;30:250-2.  Back to cited text no. 96
    
97.
Wang XH, Zhou SY, Qian ZZ, Zhang HL, Qiu LH, Song Z, et al. Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors. Expert Opin Drug Metab Toxicol 2013;9:117-25.  Back to cited text no. 97
[PUBMED]    
98.
Kashyap D, Mondal R, Tuli HS, Kumar G, Sharma AK. Molecular targets of gambogic acid in cancer: Recent trends and advancements. Tumour Biol 2016;37:12915-25.  Back to cited text no. 98
[PUBMED]    
99.
Kashyap D, Kumar G, Sharma A, Sak K, Tuli HS, Mukherjee TK. Mechanistic insight into carnosol-mediated pharmacological effects: Recent trends and advancements. Life Sci 2017;169:27-36.  Back to cited text no. 99
[PUBMED]    
100.
Kashyap D, Mittal S, Sak K, Singhal P, Tuli HS. Molecular mechanisms of action of quercetin in cancer: Recent advances. Tumour Biol 2016;37:12927-39.  Back to cited text no. 100
[PUBMED]    
101.
Kashyap D, Sharma A, Tuli HS, Sak K, Punia S, Mukherjee TK. Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements. J Funct Foods 2017;30:203-19.  Back to cited text no. 101
    
102.
Parvaresh A, Razavi R, Rafie N, Ghiasvand R, Pourmasoumi M, Miraghajani M. Quercetin and ovarian cancer: An evaluation based on a systematic review. J Res Med Sci 2016;21:34.  Back to cited text no. 102
  [Full text]  
103.
Singh B, Mense SM, Bhat NK, Putty S, Guthiel WA, Remotti F, et al. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats. Toxicol Appl Pharmacol 2010;247:83-90.  Back to cited text no. 103
[PUBMED]    


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