Abstract
Peperotetraphin (methyl rel-(1R,2S,3S)-2,3-bis(7-methoxy-1,3-benzodioxol-5-yl) cyclobutanecarboxylate) was a novel cyclobutane-type norlignan, which was isolated from the whole plant of Peperomia tetraphylla. In this study, we explored its anti-tumor effect and the molecular mechanism in human prostate cancer PC-3 cell lines. Firstly, cell viability was evaluated by Cell Counting Kit (CCK-8) assay. The PC-3 cells were treated with increasing concentrations of peperotetraphin for 24, 48 and 72 h, respectively. The results showed that peperotetraphin inhibited the growth of PC-3 cell in a dose- and time-dependent manner. Next, the cell cycle distributions were analyzed by flow cytometric analysis (FCM), and the data suggested that peperotetraphin could significantly induce cell cycle arrested at the G1–S phase transition. Then, the cell apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and annexin V-FITC/PI dual staining analysis, the data confirmed apoptosis-inducing activity of peperotetraphin and the apoptosis rates increased from 3.9 to 32.3 % when treated with increasing concentrations of peperotetraphin from 0 to 50 µM. The expression levels of apoptosis-regulating protein caspase-3, Bax and Bcl-2 were also analyzed by Western blot analysis. The results showed that the expression levels of Bax and the activity of caspase-3 were upregulated, whereas the expression levels of Bcl-2 were downregulated compared with those of the control. These findings demonstrated that peperotetraphin exhibited effective cell growth inhibition by inducing cancer to undergo G1 phase arrest and apoptosis. The results suggested that peperotetraphin might have potential as chemoprevention or anti-tumor agent to prostatic cancer.
References
Siegel R, Naishadham D, Jemal A. Cancer Stat. 2012;62:10–29.
Devlin HL, Mudryj M. Progression of prostate cancer: multiple pathways to androgen independence. Cancer Lett. 2009;2009(274):177–86.
Bhandari MS, Petrylak DP, Hussain M. Clinical trials in metastatic prostate cancer–has there been real progress in the past decade. Eur J Cancer. 2005;41:941–53.
Umezawa T. Diversity in lignan biosynthesis. Phytochem Rev. 2003;2:371–90.
Nagar N, Jat RK, Saharan R, Verma S, Sharma D, Bansal K. Podophyllotoxin and their glycosidic derivatives. Pharmacophore. 2011;2:124–34.
Delectis Florae Reipublicae Popularis Sinicae Agendae Academiae Sinicae Edita. Flora Reipublicae Popularis Sinicae. vol. 20. Beijing: Science Press; 1982. p. 70.
Li N, Wu JL, Hasegawa T, Sakai J, Bai LM, Wang LY, Kakuta S, Furuya Y, Ogura H, Kataoka T, Tomida A, Tsuruo T, Ando M. Bioactive lignans from peperomia duclouxii. J Nat Prod. 2007;70:544–8.
Li YZ, Huang J, Gong Z, Tian XQ. A Novel Norlignan and a Novel Phenylpropanoid from Peperomia tetraphylla. Helv Chim Acta. 2007;90:2222–6.
Li N, Fu HJ, Tie Y, Hu Z, Kong W, Wu YG, Zheng XF. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44–53.
Darzynkiewicz Z, Galkowski D, Zhao H. Analysis of apoptosis by cytometry using TUNEL assay. Methods. 2008;44:250–4.
Kiechle FL, Zhang X. Apoptosis: biochemical aspects and clinical implications. Clin Chim Acta. 2002;326:27–45.
Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, Kitada S, Reed JC. Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol. 1996;148:1567–76.
Borner C. The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions. Mol Immunol. 2003;39:615–47.
Krysko DV, Vanden Berghe T, D’Herde K, Vandenabeele P. Apoptosis and necrosis: detection, discrimination and phago-cytosis. Methods. 2008;44:205–21.
Kim R, Tanabe K, Uchida Y, Emi M, Inoue H, Toge T. Current status of the molecular mechanisms of anticancer drug-induced apoptosis. The contribution of molecular-level analysis to cancer chemotherapy. Cancer Chemother Pharmacol. 2002;50:343–52.
Carnero A. Targeting the cell cycle for cancer therapy. Br J Cancer. 2002;87:129–33.
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This study was supported by Anhui University of Chinese medicine (2012 RCJJ).
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Li, Y., He, N. & Zhai, C. Peperotetraphin inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and apoptosis. Med Oncol 32, 22 (2015). https://doi.org/10.1007/s12032-014-0468-8
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DOI: https://doi.org/10.1007/s12032-014-0468-8