Triptolide: A Critical Review on Antiangiogenesis in Cancer and Scope in Therapeutics

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Triptolide (TPL) is a traditional Chinese medicine and an active component of a Chinese herb Tripterygium wilfordii F. (Celastraceae). Triptolide has been used to treat a variety of ailments, including rheumatoid arthritis, nephritic syndrome and Lupus erythematosus. It is also a strong antitumor agent. Several angiogenesis assays in numerous research studies have shown that triptolide is an angiogenesis inhibitor. Numerous preclinical studies have shown that TPL inhibits cell proliferation, induces apoptosis and limits tumor metastasis. TPL also has a synergistic action with other treatment methods whereby, it enhances the effects of other antitumor treatments, as studied in various cancer cell lines. This review summarizes the recent developments and discussion of antiangiogenic mechanisms of TPL in cancer, brief outline of its clinical trials and its future in cancer therapeutics.

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Pages:

37-46

DOI:

10.4028/www.scientific.net/JBBBE.23.37

Citation:

A. Naila and Y. F. Zhang, "Triptolide: A Critical Review on Antiangiogenesis in Cancer and Scope in Therapeutics", Journal of Biomimetics, Biomaterials and Biomedical Engineering, Vol. 23, pp. 37-46, 2015

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June 2015

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$35.00

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[1] Lin, N., Sato, T., Ito, A., 2001. Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook f., suppresses the production and gene expression of pro–matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts. Arthritis & Rheumatism. 44, 2193–2200.

DOI: 10.1002/1529-0131(200109)44:9<2193::aid-art373>3.0.co;2-5

[2] Leuenroth, S.J., Okuhara, D., Shotwell, J.D., Markowitz, G.S., Yu, Z., Somlo, S., Crews, C.M., 2007. Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease. Proceedings of the National Academy of Sciences 104, 4389–4394.

DOI: 10.1073/pnas.0700499104

[3] Zheng, Y., Zhang, W.J., Wang, X.M., 2013. Triptolide with potential medicinal value for diseases of the central nervous system. CNS Neuroscience & Therapeutics 19, 76–82.

DOI: 10.1111/cns.12039

[4] Wen, H.L., Liang, Z.S., Zhang, R., Yang, K., 2013. Anti-inflammatory effects of triptolide improve left ventricular function in a rat model of diabetic cardio-myopathy. CardiovascularDiabetology12, 1–11.

[5] Tao, R., Lu, L., Zhang, R.Y., Hu, J., Ni, J.W., Shen, W.F., 2011. Triptolide inhibits rat vascular smooth muscle cell proliferation and cell cycle progression via attenuation of ERK1/2 and Rb phosphorylation. Experimental and Molecular Pathology 90, 137–142.

DOI: 10.1016/j.yexmp.2010.12.001

[6] Chen, B. J. Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook f. Leuk. Lymphoma 42: 253–265; (2001).

DOI: 10.3109/10428190109064582

[7] Qiu, D. Kao, P. N. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook f. Drugs R D 4: 1–18; (2003).

DOI: 10.2165/00126839-200304010-00001

[8] Yang S, Chen J, Guo Z, et al. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther 2003, 2: 65-72.

[9] Wu, R., Li, Y., Guo, Z., Gong, J.F., Zhu, W. M., Li, N., Li, J.S., 2013. Triptolide ameliorates ileo colonic anastomosis inflammation in IL-10deficient mice by mechanism involving suppression of miR-155/SHIP-1 signaling pathway. Molecular Immunology 56, 340–346.

DOI: 10.1016/j.molimm.2013.05.006

[10] Phillips, P.A., Dudeja, V., McCarroll, J.A., Borja-Cacho, D., Dawra, R.K., Grizzle, W.E., Vickers, S.M., Saluja, A.K., 2007. Triptolide induces pancreatic cancer cell death via inhibition of Heat Shock Protein 70. Cancer Research 67, 9407–9416.

DOI: 10.1158/0008-5472.can-07-1077

[11] Wu, P.P., Liu, K.C., Huang, W.W., Ma, C.Y., Lin, H., Yang, J.S., Chung, J.G., 2011. Triptolide induces apoptosis in human adrenal cancer NCI-H295 cells through a mitochondrial-dependent pathway. Oncology Reports25, 551–557.

DOI: 10.3892/or.2010.1080

[12] Banerjee, S., Sangwan, V., McGinn, O., Chugh,R., Dudeja, V., Vickers, S.M., Saluja, A.K., 2013. Triptolide-induced cell death in pancreatic cancer is mediated by O-G lcNAc modification of transcription factors p.1.

DOI: 10.1074/jbc.m113.500983

[13] Fang. M, Huang. Y. H, Wu Li, Ge W., Shaw. P., But. P-H, 2010. Triptolide functions as a potent angiogenesis inhibitor. Int. J. Cancer: 126, 266–278.

[14] Ma. Jian-Xia, Sun Y-L., Wang. Y-Q., Wu H U., Jin J, Yu. X.F. 2013. Triptolide Induces Apoptosis and Inhibits the Growth and Angiogenesis of Human Pancreatic Cancer Cells by Downregulating COX-2 and VEGF. Oncology Research, Vol. 20, p.359–368.

DOI: 10.3727/096504013x13657689382932

[15] Zhu. W, Ou. Y, Li. Y, Xiao. R, Shu. M, Xie J, He S., Qiu P., Yan G. 2009. A Small-Molecule Triptolide Suppresses Angiogenesis and Invasion of Human Anaplastic Thyroid Carcinoma Cells via Down-Regulation of the Nuclear Factor-kB Pathway. Mol Pharmacol 75: 812–819.

DOI: 10.1124/mol.108.052605

[16] He. M-F, Liu L, Ge W, Shaw P. C, Jiang R, Wu L. W, But P. Antiangiogenic activity of Tripterygium wilfordii and its terpenoids. Journal of Ethnopharmacology 121 (2009) 61–68.

DOI: 10.1016/j.jep.2008.09.033

[17] Li, R.W. et al. (2003) Anti-inflammatory activity of Chinese medicinal vine plants. J. Ethnopharmacol. 85, 61–67.

[18] Liu J., Shen M, Yue Z, Yang Z, Wang M, Li C, Xin C, Wang Y, Mei Q, Wang Z. Triptolide inhibits colon-rectal cancer cells proliferation by induction of G1 phase arrest through upregulation of p.21. Phytomedicine 19 (2012) 756– 762.

DOI: 10.1016/j.phymed.2012.02.014

[19] Koo HS, Kang SD, Le JH, Kim NH, Chung HT, Pae HO. Triptolide inhibits the proliferation of immortalized HT22 hippocampal cells via persistent activation of extracellular signal-regulated kinase-1/2 by down-regulating mitogen-activated protein kinase phosphatase-1 expression. J Korean Neurosurg Soc 2009, 46: 389–96.

DOI: 10.3340/jkns.2009.46.4.389

[20] Bacus SS, Gudkov AV, Lowe M, et al: Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p.38) and is independent of p.53. Oncogene 20: 147-155, (2001).

DOI: 10.1038/sj.onc.1204062

[21] Tang D, Wu D, Hirao A, et al: ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p.53. J Biol Chem 277: 12710-12717, (2002).

DOI: 10.1074/jbc.m111598200

[22] Yang S., Gu C, Zhang G, Kang J, Wen H, Lu Q, Huang J. Inhibitive effect of triptolide on invasiveness of human fibrosarcoma cells by downregulating matrix metalloproteinase-9 expression. Asian Pacific Journal of Tropical Medicine (2011)482-485.

DOI: 10.1016/s1995-7645(11)60131-4

[23] Wang C, Shan Y, Yang JL, et al. Inhibition of Cancer Angiogenesis Using Triptolide Nanoparticles[J]. Journal of Biomedical Nanotechnology, 2015, 11(5): 805-815.

[24] Folkman, J. (1971) Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182–1186.

[25] Fan T. P, Yeh J. C, Leung K. W, Y.K. Patrick, Wong Ricky N.S. Angiogenesis: from plants to blood Vessels. Vol. 27 No. 6 June (2006).

[26] Meng Cuicui, et. al. Targets and molecular mechanisms of triptolide in cancer therapy. Chin J Cancer Res 2014, 26(5): 622-626.

[27] Coultas, L., Chawengsaksophak, K., Rossant, J., 2005. Endothelial cells and VEGF in vascular development. Nature 438, 937–945.

DOI: 10.1038/nature04479

[28] He MF, Huang YH, Wu LW, et al. Triptolide functions as a potent angiogenesis inhibitor. Int J Cancer 2010, 126: 266-78.

[29] Li, S. et al. (2003) Suppressive effects of a Chinese herbal medicine qing-luo-yin extract on the angiogenesis of collagen-induced arthritis in rats. Am. J. Chin. Med. 31, 713–720.

DOI: 10.1142/s0192415x03001430

[30] Ferrara N, Gerber HP, and LeCouter J (2003). The biology of VEGF and its receptors. Nat Med 9: 669–676.

DOI: 10.1038/nm0603-669

[31] Schmitt M, Horbach A, Kubitz R, Frilling A, and Ha¨ussinger D (2004) Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion. J Hepatol 41: 274–283.

DOI: 10.1016/j.jhep.2004.04.035

[32] Weis S, Cui J, Barnes L, and Cheresh D (2004) Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol 167: 223–229.

DOI: 10.1083/jcb.200408130

[33] Hu, K.B. et al. (2002) Inhibition of vascular endothelial growth factor expression and production by triptolide. Planta Med. 68, 368–369.

DOI: 10.1055/s-2002-26737

[34] Wang, B. et al. (2004).

[35] Kato, H., Yoshikawa, M., Miyazaki, T., Nakajima, M., Fukai, Y., Masuda, N., Fukuchi, M.; Manda, R., Tsukada, K., Kuwano, H. Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) in esophageal squamous cell carcinoma. Anticancer Res. 22: 3977–3984. (2002).

DOI: 10.1002/ijc.11651

[36] Saad, R. S., El-Gohary, Y., Memari, E., Liu, Y. L., Silverman, J. F. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma. Hum. Pathol. 36: 955–961. (2005).

DOI: 10.1016/j.humpath.2005.06.019

[37] Patard, J. J., Rioux-Leclercq, N., Masson, D., Zerrouki, S., Jouan, F., Collet, N., Dubourg, C., Lobel, B., Denis, M., Fergelot, P. Absence of VHL gene alteration and high VEGF expression are associated with tumour aggressiveness and poor survival of renal-cell carcinoma. Br J. Cancer 101: 1417–1424, (2009).

DOI: 10.1038/sj.bjc.6605298

[38] Wu, Y., Jin, M., Xu, H., Shimin, Z., He, S., Wang, L., Zhang, Y. Clinicopathologic significance of HIF-1a, CXCR4, and VEGF expression in colon cancer. Clin. Dev. Immunol. Pii : 537531, (2010).

DOI: 10.1155/2010/537531

[39] . Johnson, S. M., Wang, X., Evers, B. M. Triptolide inhibits proliferation and migration of colon cancer cells by inhibition of cell cycle regulators and cytokine receptors. J. Surg. Res. 168: 197–205, (2011).

DOI: 10.1016/j.jss.2009.07.002

[40] Okami, J., Yamamoto, H., Fujiwara, Y., Tsujie, M., Kondo, M., Noura, S., Oshima, S., Nagano, H., Dono, K., Umeshita, K., Ishikawa, O., Sakon, M., Matsuura, N., Nakamori, S., Monden, M. Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. Clin. Cancer Res. 5: 2018–2024, (1999).

DOI: 10.1023/a:1027319903359

[41] Petkova, D. K., Clelland, C., Ronan, J., Pang, L., Coulson, J. M., Lewis, S., Knox, A. J. Overexpression of cyclooxygenase- 2 in non-small cell lung cancer. Respir. Med. 98: 164–172, (2004).

DOI: 10.1016/j.rmed.2003.09.006

[42] Wang, D., Dubois, R. N. Cyclooxygenase-2: A potential target in breast cancer. Semin. Oncol. 31: 6473, (2004).

[43] Gately, S. The contributions of cyclooxygenase-2 to tumor angiogenesis. Cancer Metastasis Rev. 19: 19–27, (2000).

[44] Chilov D, Kukk E, Taira S, Jeltsch M, Kaukonen J, Palotie A, Joukov V, and Alitalo K (1997) Genomic organization of human and mouse genes for vascular endothelial growth factor C. J Biol Chem 272: 25176–25183.

DOI: 10.1074/jbc.272.40.25176

[45] Manning, B.D., Cantley L.C., 2007. AKT/PKB signaling: navigating downstream. Cell 129, 1261–1274.

DOI: 10.1016/j.cell.2007.06.009

[46] Tai CJ, Wu AT, Chiou JF, Jan HJ, Wei HJ, Hsu CH, et al. The investigation of mitogen activated protein kinase phosphatase-1 as a potential pharmacological target in non-small cell lung carcinomas, assisted by non-invasive molecular imaging. BMC Cancer 2010, 10: 95–109.

DOI: 10.1186/1471-2407-10-95

[47] Koo HS, Kang SD, Lee JH, Kim NH, Chung HT, Pae HO. Triptolide inhibits the proliferation of immortalized HT22 hippocampal cells via persistent activation of extracellular signal-regulated kinase-1/2 by down-regulating mitogen-activated protein kinase phosphatase-1 expression. J Korean Neurosurg Soc 2009, 46: 389–96.

DOI: 10.3340/jkns.2009.46.4.389

[48] Miyata Y, Sato T, Ito A. Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH2-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells. Biochem BiophysRes Commun 2005, 336: 1081–6.

DOI: 10.1016/j.bbrc.2005.08.247

[49] Yang SB, Wen HQ, Zhang GY, Zhao S, Luo YQ, Lu QJ. Triptolide elevates the DNA methyation level of metrix metalloproteinase-9 gene in human fibrosarcoma HT-1080 cells. Zhongguo Zhong Yao Za Zhi 2009, 34(5): 611-614.

[50] Kitzen JJ, de Jonge MJ, Lamers CH, et al. Phase I dose-escalation study of F60008, a novel apoptosis inducer, in patients with advanced solid tumours. Eur J Cancer 2009; 45: 1764-72.

DOI: 10.1016/j.ejca.2009.01.026

[51] Li X. J, Jiang Z-Z, Zhang Lu-Y. Triptolide: Progress on research in pharmacodynamics and toxicology . Journal of Ethnopharmacology155(2014)67–79.

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