Abstract
Cucurbitacin D, a newly isolated triterpenoid cucurbitacin, has been found to possess anticancer effects. The purpose of this study was to elucidate the effects of cucurbitacin D on human endometrial and ovarian cancer cells. Human endometrial and ovarian cancer cells were treated with various concentrations of cucurbitacin D, and its effects on cell growth, the cell cycle, apoptosis, and their related measurements were investigated in vitro. All endometrial and ovarian cancer cell lines were sensitive to the growth-inhibitory effect of cucurbitacin D. Cell cycle analysis indicated that their exposure to cucurbitacin D increased the proportion in the sub-G0/G1 phases and G2/M phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and loss of the transmembrane potential of mitochondria. This induction occurred in concert with altered expression of genes related to cell growth, malignant phenotype, and apoptosis. Our results suggest that cucurbitacin D might be a new therapeutic option for the treatment of endometrial and ovarian cancers.
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References
Reinhardt MJ. Gynecologic tumors. Recent Results Cancer Res. 2008;170:141–50.
Obel JC, Friberg G, Fleming GF. Chemotherapy in endometrial cancer. Clin Adv Hematol Oncol. 2006;4:459–68.
Winter 3rd WE, Maxwell GL, Tian C, et al. Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2008;26:83–9. doi:10.1200/JCO.2007.13.1953.
Jayaprakasam B, Seeram NP, Nair MG. Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana. Cancer Lett. 2003;189:11–6.
Chen JC, Chiu MH, Nie RL, et al. Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep. 2005;22:386–99. doi:10.1039/B418841C.
Takahashi N, Yoshida Y, Sugiura T, et al. Cucurbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma cells in vitro. Int Immunopharmacol. 2009;9:508–13.
Ding N, Yamashita U, Matsuoka H, et al. Apoptosis induction through proteasome inhibitory activity of cucurbitacin D in human T-cell leukemia. Cancer. 2011;117:2735–46. doi:10.1002/cncr.25711.
Rimon G, Bazenet CE, Philpott KL, et al. Increased surface phosphatidylserine is an early marker of neuronal apoptosis. J Neurosci Res. 1997;48:563–70. doi:10.1002/(SICI)1097-4547.
Chen Y, Kramer DL, Diegelman P, et al. Apoptotic signaling in polyamine analogue-treated SK-MEL-28 human melanoma cells. Cancer Res. 2001;61:6437–44.
Abukhdeir AM, Park BH. P21 and p27: roles in carcinogenesis and drug resistance. Expert Rev Mol Med. 2008;10:e19.
Kelly PN, Strasser A. The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ. 2011;18:1414–24. doi:10.1038/cdd.2011.17.
Johnson DG, Walker CL. Cyclins and cell cycle checkpoints. Ann Rev Pharmacol Toxicol. 1999;39:295–312.
Tretiakova I, Blaesius D, Maxia L, et al. Myrtucommulone from Myrtus communis induces apoptosis in cancer cells via the mitochondrial pathway involving caspase-9. Apoptosis. 2008;13:119–31.
Liu K, Xing H, Xhang S, et al. Cucurbitacin D induces fetal hemoglobin synthesis in K562 cells and human hematopoietic progenitors through activation of p38 pathway and stabilization of the γ-globin mRNA. Blood Cells Mol Dis. 2010;45:269–75. doi:10.1016/j.bcmd.2010.09.004.
Blaskovich MA, Sun J, Cantor A, et al. Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res. 2003;63:1270–9.
Konopa J, Matuszkiewicz A, Hrabowska M. Cucurbitacines, cytotoxic and antitumor substances from Bryonia alba L. Part II: Biological studies. Arzneimittelforschung. 1974;24:1741–3.
Konopa J, Zielinski J, Matuszkiewicz A. Cucurbitacins, cytotoxic and antitumor substances from Bryonia alba L. I: isolation and identification. Arzneimittelforschung. 1974;24:1554–7.
Park CS, Lim H, Han KJ, et al. Inhibition of nitric oxide generation by 23,24-dihydrocucurbitacin D in mouse peritoneal macrophages. J Pharmacol Exp Ther. 2004;309:705–10. doi:10.1124/jpet.103.063693.
Acknowledgments
We sincerely thank Ms. Satoko Koga for her technical assistances. This study was supported by a Research Fund at the Discretion of the President, Oita University (HN).
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Ishii, T., Kira, N., Yoshida, T. et al. Cucurbitacin D induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial and ovarian cancer cells. Tumor Biol. 34, 285–291 (2013). https://doi.org/10.1007/s13277-012-0549-2
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DOI: https://doi.org/10.1007/s13277-012-0549-2