Abstract
Objective
Jatropha curcashas been used in traditional medicine in Africa to treat cancer for thousands of years. This study aimed to examine the anti-endometrial cancer effect of Curcusone C, a naturally occurring rhamnofolane diterpene, isolated from J. curcas and reveal its molecular mechanism of action.
Results
Curcusone C treatment caused significant anti-proliferative and apoptotic effects in human endometrial cancer (EC) Ishikawa and HEC-1A cells in a dose-dependent manner. Exposure of EC cells to Curcusone C resulted in apoptosis, which was associated with cytochrome c release, caspase-3 and caspase-9 activation, Bcl-xL/Bax dysregulation, and decreased expression of inhibitors of apoptosis proteins, such as XIAP and survivin. The inhibitory effect induced by Curcusone C was greatly impaired by the overexpression of survivin or Bax−/− MEFs or the knockdown of Bim expression. Moreover, Curcusone C activated mitogen-activated protein kinases, and the ERK inhibitor U0126 significantly attenuated the growth-inhibitory and apoptotic effects of Curcusone C in Ishikawa cells.
Conclusion
Taken together, the results demonstrate the anti-endometrial cancer potential of Curcusone C for the treatment of endometrial cancer.
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References
Ai Z, Yin L, Zhou X, Zhu Y, Zhu D, Yu Y, Feng Y (2006) Inhibition of survivin reduces cell proliferation and induces apoptosis in human endometrial cancer. Cancer 107(4):746–756
Aiyelaagbe OO, Hamid AA, Fattorusso E, Taglialatela-Scafati O, Schröder HC, Müller WEG (2011) Cytotoxic activity of crude extracts as well as of pure components from species, plants used extensively in African traditional medicine. Evid-Based Complement Altern Med 2011:1–7
Altieri DC (2003) Validating survivin as a cancer therapeutic target. Nat Rev Cancer 3:46–54. https://doi.org/10.1038/nrc968
Choi J, Chun K, Kundu J, Kundu J (2013) Biochemical basis of cancer chemoprevention and/or chemotherapy with ginsenosides (review). Int J Mol Med 32:1227–1238. https://doi.org/10.3892/ijmm.2013.1519
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337
Fister S, Günthert AR, Aicher B, Paulini KW, Emons G, Gründker C (2009) GnRH-II antagonists induce apoptosis in human endometrial, ovarian, and breast cancer cells via activation of stress-induced MAPKs p38 and JNK and proapoptotic protein Bax. Cancer Res 69:6473–6481. https://doi.org/10.1158/0008-5472
Goyal S, Gupta N, Chatterjee S, Nimesh S (2017) Natural plant extracts as potential therapeutic agents for the treatment of cancer. Curr Top Med Chem 17:96–106. https://doi.org/10.2174/1568026616666160530154407
Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312. https://doi.org/10.1126/science.281.5381.1309
Gross A (2001) Bcl-2 proteins: regulators of the mitochondrial apoptotic program. IUBMB Life 52:231–236. https://doi.org/10.1080/15216540152846046
Holcik M (2003) Translational upregulation of the X-linked inhibitor of apoptosis. Ann N Y Acad Sci 1010:249–258. https://doi.org/10.1196/annals.1299.043
Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, Sasaki T, Elia AJ, Cheng HY, Ravagnan L, Ferri KF, Zamzami N, Wakeham A, Hakem R, Yoshida H, Kong YY, Mak TW, Zuniga-Pflücker JC, Kroemer G, Penninger JM (2001) Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 140:549–554. https://doi.org/10.1038/35069004
Kim H, Rafiuddin-Shah M, Tu HC, Jeffers JR, Zambetti GP, Hsieh JJ, Cheng EH (2006) Hierarchical regulation of mitochondrialdependent apoptosis by BCL-2 subfamilies. Nat Cell Biol 8:1348–1358. https://doi.org/10.1038/ncb1499
Lappano R, Sebastiani A, Cirillo F, Rigiracciolo DC, Galli GR, Curcio R, Malaguarnera R, Belfiore A, Cappello AR, Maggiolini M (2017) The lauric acid-activated signaling prompts apoptosis in cancer cells. Cell Death Discov 3:17063–17080
Maravi DK, Mazumdar P, Alam S, Goud VV, Sahoo L (2015) Jatropha (Jatropha curcas L.). Methods Mol Biol 1224:25–35. https://doi.org/10.1007/978-1-4939-1658-0_3
Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E (2016) Endometrial cancer. Lancet 387:1094–1108. https://doi.org/10.1016/S0140-6736(15)00130-0
Ngamkham WNJ, Rienkitjakarn M, Picha P (2010) Induction of apoptosis by purified compound from Jatropha curcas in breast cancer cell. Thai Cancer J 29:90–101
Park GB, Kim YS, Lee HK, Song H, Cho DH, Lee WJ, Hur DY (2010) Endoplasmic reticulum stress-mediated apoptosis of EBV-transformed B cells by cross-linking of CD70 is dependent upon generation of reactive oxygen species and activation of p38 MAPK and JNK pathway. J Immunol 185:7274–7284. https://doi.org/10.4049/jimmunol
Rabi T, Bishayee A (2009) Terpenoids and breast cancer chemoprevention. Breast Cancer Res Treat 115:223–239. https://doi.org/10.1007/s10549-008-0118-y
Shin S, Sung BJ, Cho YS, Kim HJ, Ha NC, Hwang JI, Chung CW, Jung YK, Oh BH (2001) An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7. Biochemistry 40:1117–1123. https://doi.org/10.1021/bi001603q
Wang M, Cao J, Zhu JY, Qiu J, Zhang Y, Shu B, Ou TM, Tan JH, Gu LQ, Huang ZS, Yin S, Li D (2017) Curcusone C induces telomeric DNA-damage response in cancer cells through inhibition of telomeric repeat factor 2. Biochim Biophys Acta Proteins Proteom 1865:1372–1382. https://doi.org/10.1016/j.bbapap.2017.08.022
Wang Y, Wang Y, Duan X, Wang Y, Zhang Z (2018) Interleukin-1 receptor-associated kinase 1 correlates with metastasis and invasion in endometrial carcinoma. J Cell Biochem 119:2545–2555. https://doi.org/10.1002/jcb.26416
Wong RS (2011) Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 30:87. https://doi.org/10.1186/1756-9966-30-87
Wu HM, Cheng JC, Wang HS, Huang HY, MacCalman CD, Leung PC (2009) Gonadotropin-releasing hormone type II induces apoptosis of human endometrial cancer cells by activating GADD45alpha. Cancer Res 69:4202–4208. https://doi.org/10.1158/0008-5472.CAN-08-459
Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Greenberg ME: opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326–1331. https://doi.org/10.1126/science.270.5240.1326
Zhang XL, Li F, Zhao ZG, Liu XL, Tang YX, Wang MK (2012) Diterpenoids from the root bark of Jatropha curcas and their cytotoxic activities. Phytochem Lett 5:721–724. https://doi.org/10.1016/j.phytol.2012.07.011
Zhu Q, An J, Li F, Wang M, Wu J, Tang Y (2013) Curcusone C induces apoptosis in human ovarian cancer SK-OV-3 cells. Chin J Appl Environ Biol 19:956–959
Zou W, Zeng J, Zhuo M, Xu W, Sun L, Wang J, Liu X (2002) Involvement of caspase-3 and p38 mitogen-activated protein kinase in cobalt chloride-induced apoptosis in PC12 cells. J Neurosci Res 67:837–843. https://doi.org/10.1002/jnr.10168
Acknowledgements
This work was financially supported by the Lanzhou Science and Technology Bureau (Grant No. 2017-4-55).
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An, J., Li, L. & Zhang, X. Curcusone C induces apoptosis in endometrial cancer cells via mitochondria-dependent apoptotic and ERK pathway. Biotechnol Lett 43, 329–338 (2021). https://doi.org/10.1007/s10529-020-03027-4
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DOI: https://doi.org/10.1007/s10529-020-03027-4