Research progress of ursolic acid’s anti-tumor actions

Li-li Zang; Bao-ning Wu; Yuan Lin; Jun Wang; Lei Fu; Ze-yao Tang

doi:10.1007/s11655-013-1541-4

Your Location：

Home >

Browse articles >

Research progress of ursolic acid’s anti-tumor actions

ReviewPaper | Updated：2021-08-27

- Research progress of ursolic acid’s anti-tumor actions
- Research progress of ursolic acid’s anti-tumor actions
- 中国结合医学杂志（英文版） 2014年20卷第1期页码：72-79
- Affiliations：
  
  Pharmacology Department, Dalian Medical University,Liaoning Province,Dalian,China
- Author bio：
- Funds：
  
  Supported by the National Natural Science Foundation of China ( No. 30772601)
- DOI：10.1007/s11655-013-1541-4
  中图分类号：
- 纸质出版日期：2014，
  
  网络出版日期：2013-12-29，
Scan for full text
Zang, Ll., Wu, Bn., Lin, Y. et al. Research progress of ursolic acid’s anti-tumor actions., Chin. J. Integr. Med. 20, 72–79 (2014). https://doi.org/10.1007/s11655-013-1541-4

Li-li Zang, Bao-ning Wu, Yuan Lin, et al. Research progress of ursolic acid’s anti-tumor actions[J]. Chinese Journal of Integrative Medicine, 2014,20(1):72-79.
Zang, Ll., Wu, Bn., Lin, Y. et al. Research progress of ursolic acid’s anti-tumor actions., Chin. J. Integr. Med. 20, 72–79 (2014). https://doi.org/10.1007/s11655-013-1541-4 DOI：

Li-li Zang, Bao-ning Wu, Yuan Lin, et al. Research progress of ursolic acid’s anti-tumor actions[J]. Chinese Journal of Integrative Medicine, 2014,20(1):72-79. DOI： 10.1007/s11655-013-1541-4.

摘要

Ursolic acid (UA) is a sort of pentacyclic triterpenoid carboxylic acid purified from natural plant. UA has a series of biological effects such as sedative

anti-inflammatory

anti-bacterial

anti-diabetic

antiulcer

etc. It is discovered that UA has a broad-spectrum anti-tumor effect in recent years

which has attracted more and more scholars’ attention. This review explained anti-tumor actions of UA

including (1) the protection of cells’ DNA from different damages; (2) the anti-tumor cell proliferation by the inhibition of epidermal growth factor receptor/mitogen-activated protein kinase signal or of FoxM1 transcription factors

respectively; (3) antiangiogenesis

(4) the immunological surveillance to tumors; (5) the inhibition of tumor cell migration and invasion; (6) the effect of UA on caspase

cytochromes C

nuclear factor kappa B

cyclooxygenase

tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or mammalian target of rapamycin signal to induce tumor cell apoptosis respectively

and etc. Moreover

UA has selective toxicity to tumor cells

basically no effect on normal cells. With further studies

UA would be one of the potential anti-tumor agents.

Abstract

Ursolic acid (UA) is a sort of pentacyclic triterpenoid carboxylic acid purified from natural plant. UA has a series of biological effects such as sedative

anti-inflammatory

anti-bacterial

anti-diabetic

antiulcer

etc. It is discovered that UA has a broad-spectrum anti-tumor effect in recent years

which has attracted more and more scholars’ attention. This review explained anti-tumor actions of UA

respectively; (3) antiangiogenesis

(4) the immunological surveillance to tumors; (5) the inhibition of tumor cell migration and invasion; (6) the effect of UA on caspase

cytochromes C

nuclear factor kappa B

cyclooxygenase

tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or mammalian target of rapamycin signal to induce tumor cell apoptosis respectively

and etc. Moreover

UA has selective toxicity to tumor cells

basically no effect on normal cells. With further studies

UA would be one of the potential anti-tumor agents.

关键词

Ursolic Acidanti-tumorresearch progress

Keywords

Ursolic Acidanti-tumorresearch progress

references

Wu B, Wang X, Wang HH, et al. Apoptosis of jurkat cells induced by ursolic acid and its mechanison. Chin J Integr West Chin Med (Chin) 2010;18:61–66.

Paz-Elizur T, Sevilya Z, Leitner-Dagan Y, Elinger D, Roisman LC, Livneh Z. DNA repair of oxidative DNA damage in human carcinogenesis: potential application for cancer risk assessment and prevention. Cancer Lett 2008;266:60–72.

Ramos AA, Lima CF, Pereira ML, Fernandes-Ferreira M, Pereira-Wilson C. Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: evaluation by the comet assay. Toxicol Lett 2008;177:66–73.

Ramos AA, Pereira-Wilson C, Collins AR. Protective effects of ursolic acid and Luteolin against oxidative DNA damage include enhancement of DNA repair in Caco-2 cells. Mutat Res 2010;692:6–11.

Messner B, Zeller I, Ploner C, Frotschnig S, Ringer T, Steinacher-Nigisch A, et al. Ursolic acid causes DNAdamage, P53-mediated, mitochondria- and caspasedependent human endothelial cell apoptosis, and accelerates atherosclerotic plaque formation in vivo. Atherosclerosis 2011;219:402–408.

Park KS, Kim NG, Kim JJ, Kim H, Ahn YH, Choi KY. Differential regulation of MAP kinase cascade in human colorectal tumorigenesis. Br J Cancer 1999;81:1116–1121.

Yong HY, Koh MS, Moon A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin Investig Drugs 2009;18:1893–1905.

Calvo F, Agudo-Ibáñez L, Crespo P. The Ras-ERK pathway: understanding site-specific signaling provides hope of new anti-tumor therapies. Bioessays 2010;32:412–421.

Achiwa Y, Hasegawa K, Udagawa Y. Regulation of the phosphatidylinositol 3-kinase-Akt and the mitogenactivated protein kinase pathways by ursolic acid in human endometrial cancer cells. Biosci Biotechnol Biochem 2007;71:31–37.

Shan JZ, Xuan YY, Zheng S, Dong Q, Zhang SZ. Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibiting the EGFR/MAPK pathway. J Zhejiang Univ Sci B 2009;10:668–674.

Wang X, Li L, Wang B, Xiang J. Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells. Huazhong Univ Sci Technolog Med Sci (Chin) 2009;29:761–764.

Kanjoormana M, Kuttan G. Anti-angiogenic activity of ursolic acid. Integr Cancer Ther 2010;9:224–235.

Gartel AL. A new target for proteasome inhibitors: FoxM1. Expert Opin Investig Drugs 2010;19:235–242.

Wang JS, Ren TN, Xi T. Ursolic acid induces apoptosis by suppressing the expression of FoxM1 in MCF-7 human breast cancer cells. Med Oncol 2010 Dec 30.

Bonaccorsi I, Altieri F, Sciamanna I, Oricchio E, Grillo C, Contartese G, et al. Endogenous reverse transcriptase as a mediator of ursolic acid’s anti-proliferative and differentiating effects in human cancer cell lines. Cancer Lett 2008;263:130–139.

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;59:755–762.

Cha DS, Shin TY, Eun JS, Kim DK, Jeon H. Anti-metastatic properties of the leaves of Eriobotrya japonica. Arch Pharm Res 2011;34:425–436.

Hallam S, Escorcio-Correia M, Soper R, Schultheiss A, Hagemann T. Activated macrophages in the tumour microenvironment — dancing to the tune of TLR and NF-κB. J Pathol 2009;219:143–152.

Jung TY, Pham TN, Umeyama A, Shoji N, Hashimoto T, Lee JJ, et al. Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells. Eur J Pharmacol 2010;643:297–303.

Klein G, Vellenga E, Fraaije MW, Kamps WA, de Bont ES. The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol 2004;50:87–100.

Margheri F, D’Alessio S, Serratì S, Pucci M, Del Rosso A, Benelli R, et al. The urokinase-type plasminogen activator, its receptor and u-PA inhibitor type-1 affect in vitro growth and invasion of Kaposi’s sarcoma and capillary endothelial cells: role of HIV-Tat protein. Int J Oncol 2005;27:223–35.

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;54:1285–1295.

Zhang Y, Kong C, Zeng Y, Wang L, Li Z, Wang H, et al. Ursolic acid induces PC-3 cell apoptosis via activation of JNK and inhibition of Akt pathways in vitro. Mol Carcinog 2010;49:374–385.

Ruoslahti E. Vascular zip codes in angiogenesis and metastasis. Biochem Soc Trans 2004;32:397–402.

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;48:517–531

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;25:1274–1280.

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;129:1552–1563.

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;61:777–782.

Kwon SH, Park HY, Kim JY, Jeong IY, Lee MK, Seo KI. Apoptotic action of ursolic acid isolated from Corni fructus in RC-58T/h/SA#4primary human prostate cancer cells. Bioorg Med Chem Lett 2010;20:6435–6438.

Zhang GP, Lu YY, Lv JC, Ou HJ. Effect of ursolic acid on caspase-3 and PARP expression of human MCF-7 cells. China J Chin Mater Med (Chin) 2006;31:141–144.

Shyu MH, Kao TC, Yen GC. Oleanolic acid and ursolic acid induce apoptosis in HuH7 human hepatocellular carcinoma cells through a mitochondrial-dependent pathway and downregulation of XIAP. J Agric Food Chem 2010;58:6110–6118.

Constantinou C, Papas KA, Constantinou AI. Caspaseindependent pathways of programmed cell death: the unraveling of new targets of cancer therapy? Curr Cancer Drug Targets 2009;9:717–728.

Kim KH, Seo HS, Choi HS, Choi I, Shin YC, Ko SG. Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells. Arch Pharm Res 2011;34:1363–1372.

Lai MY, Leung HW, Yang WH, Chen WH, Lee HZ. Upregulation of matrix metalloproteinase family gene involvement in ursolic acid-induced human lung non-small carcinoma cell apoptosis. Anticancer Res 2007;27:145–153.

Zhang YX, Kong CZ, Wang LH, Li JY, Liu XK, Xu B, et al. Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation. J Cell Biochem 2010;109:764–773.

Liu XS, Jiang J. Induction of apoptosis and regulation of the MAPK pathway by ursolic acid in human leukemia K562 cells. Planta Med 2007;73:1192–1194.

Baud V, Jacque E. The alternative NF-kB activation pathway and cancer: friend or foe? Med Sci (Paris) 2008;24:1083–1088.

Yu YX, Gu ZL, Yin JL, Chou WH, Kwok CY, Qin ZH, et al. Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway. Chin Med J 2010;123:1915–1923.

Wang X, Li L, Wang B, Xiang J. Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells. J Huazhong Univ Sci Technolog Med Sci (Chin) 2009;29:761–764.

Duval RE, Harmand PO, Jayat-Vignoles C, Cook-Moreau J, Pinon A, Delage C, et al. Differential involvement of mitochondria during ursolic acid-induced apoptotic process in HaCaT and M4Beu cells. Oncol Rep 2008;19:145–149.

Shan JZ, Xuan YY, Ruan SQ, Sun M. Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro. Chin J Integr Med 2011;17:607–611.

Li Y, Xing D, Chen Q, Chen WR. Enhancement of chemotherapeutic agent-induced apoptosis by inhibition of NF-kappaB using ursolic acid. Int J Cancer 2010;127:462–473.

Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 2010;21:11–19.

Yu Y, Wang Z. Advances of the correlation between JAKSTAT3 signaling pathway and the biological behavior of non-small cell lung cancer. Chin J Lung Cancer (Chin) 2010;13:160–164.

Pathak AK, Bhutani M, Nair AS, Ahn KS, Chakraborty A, Kadara H, et al. Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Mol Cancer Res 2007;5:943–595.

Ghosh N, Chaki R, Mandal V, Mandal SC. COX-2 as a target for cancer chemotherapy. Pharmacol Rep 2010;62:233–244.

Zhang YY, Deng T, Hu ZF, Zhang QP, Zhang J, Jiang H. Mechanisms of inhibiting proliferation and inducing apoptosis of human gastric cancer cell line SGC7901 by ursolic acid. Chin J Cancer (Chin) 2006;25:432–437.

Limami Y, Pinon A, Leger DY, et al. HT-29 colorectal cancer cells undergoing apoptosis overexpress COX-2 to delay ursolic acid-induced cell death. Biochimie 2011;93:749–757.

Tian Z, Lin G, Zheng RX, Huang F, Yang MS, Xiao PG. Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana. World J Gastroenterol 2006;12:874–879.

Gonzalvez F, Ashkenazi A. New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene 2010;29:4752–4765.

Wang S. TRAIL: a sword for killing tumors. Curr Med Chem 2010;17:3309–3317.

Prasad S, Yadav VR, Kannappan R, Aggarwal BB. Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-Independent upregulation of death receptors: evidence for the role of reactive oxygen species and C-Jun N-terminal kinase. J Biol Chem 2011;18;286:5546–5557.

Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011;12:21–35.

Carnero A. The PKB/AKT pathway in cancer. Curr Pharm Des 2010;16:34–44.

De Angel RE, Smith SM, Glickman RD, Perkins SN, Hursting SD. Antitumor effects of ursolic acid in a mouse model of postmenopausal breastcancer. Nutr Cancer 2010;62:1074–1086.

Sultana N. Clinically useful anticancer, antitumor, and antiwrinkle agent, ursolic acid and related derivatives as medicinally important natural product. J Enzyme Inhib Med Chem 2011;26:616–642.

Li J, Guo WJ, Yang QY. Effects of ursolic acid and olenaolic acid on human coloncancinoma cell line HCT15. Word J Gastroenterol (Chin) 2002;8:4934–4995.

Wang P, Zhang ZY. The distribution and pharmacological effects of Ursolic acid in medicinal plants. J Chin Med Mater (Chin) 2000;23:717–717.

Nakajima H, Sakaguchi K, Mizuta N, Fujiwara I, Hayakawa A, Magae J. Apoptotic mechanisms induced in breast cancer cells by vinorelbine. Gan To Kagaku Ryoho (Japn) 2007;34:583–588.

Basili S, Moro S. Novel camptothecin derivatives as topoisomerase I inhibitors. Expert Opinion Therapeutic Patents 2009;19:555–574.

Yamaguchi H, Yu T, Noshita T, Kidachi Y, Kamiie K, Yoshida K, et al. Ligand-receptor interaction between triterpenoids and 11taHSD2 predicts their toxic effects against tumorigenic r/m HM-SFME-1 cells. J Biol Chem 2011;286:36888–36897.

Lu WJ, Ya QK, Chen JY, Liu BM. A new flavonol glycoside from Baeckea Frutescens L. Acta Pharmac Sin (Chin) 2008;43:1032–1035.

Yang SM, Liu XK, Qing C, Wu DG, Zhu DY. Chemical constituents from the roots of Homonoia riparia. Acta Pharmac Sin (Chin) 2007;42:292–296.

FULL TEXT LINK

More>

浏览量

745

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Ursolic acid inhibits T-cell activation through modulating nuclear factor-κ B signaling

Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro

Experimental study on apoptosis induced by ursolic acid isolated from asparagus in HL-60 cells