Ophiopogonin D inhibits cell proliferation, causes cell cycle arrest at G2/M, and induces apoptosis in human breast carcinoma MCF-7 cells

doi:10.1016/S2095-4964(16)60238-8

Abstract

Objective

To investigate the effects of ophiopogonin D on human breast cancer MCF-7 cells.

Methods

Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation experiments. Cell cycle was measured with cell cycle flow cytometry and a living cell assay. Apoptosis and terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling assays were performed to detect the apoptosis of MCF-7 cells induced by ophiopogonin D. Finally, Western blotting was used to explore the mechanism.

Results

Exposure of cells to ophiopogonin D resulted in marked decreases in viable cells and colony formation with a dose-dependent manner. Treatment of these cells with ophiopogonin D also resulted in cell cycle arrest at the G₂/M phase, and increased apoptosis. Mechanistically, ophiopogonin D-induced G₂/M cell cycle arrest was associated with down-regulation of cyclin B1. Furthermore, activation of caspase-8 and caspase-9 was involved in ophiopogonin D-induced apoptosis.

Conclusion

The data suggested that ophiopogonin D inhibits MCF-7 cell growth via the induction of cell cycle arrest at the G₂/M phase.

Key words: Ophiopogonin D, G₂/M arrest, Apoptosis, Cyclin B1, Caspases, Breast neoplasms, Antineoplastic agents, Phytogenic, In vitro

Qing-qing Zang, Lu Zhang, Ning Gao, Cheng Huang. Ophiopogonin D inhibits cell proliferation, causes cell cycle arrest at G₂/M, and induces apoptosis in human breast carcinoma MCF-7 cells. Journal of Integrative Medicine, 2016, 14(1): 51-59.

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References

1 Li Y, Li D, Yuan S, Wang Z, Tang F, Nie R, Weng J, Ma L, Tang B.Embelin-induced MCF-7 breast cancer cell apoptosis and blockade of MCF-7 cells in the G2/M phase via the mitochondrial pathway.Oncol Lett. 2013; 5(3): 1005-1009.
2 Pimhanam C, Sangrajrang S, Ekpanyaskul C.Tobacco smoke exposure and breast cancer risk in Thai urban females.Asian Pac J Cancer Prev. 2014; 15(17): 7407-7411.
3 Wang C, Pan YH, Shan M, Xu M, Bao JL, Zhao LM.Knockdown of UbcH10 enhances the chemosensitivity of dual drug resistant breast cancer cells to epirubicin and docetaxel.Int J Mol Sci. 2015; 16(3): 4698-4712.
4 Du F, Yuan P, Wang JY, Ma F, Fan Y, Luo Y, Xu BH.Effect of hormone therapy on long-term outcomes of patients with human epidermal growth factor receptor 2- and hormone receptor-positive metastatic breast cancer: real world experience in China.Asian Pac J Cancer Prev. 2015; 16(3): 903-907.
5 Shajahan-Haq AN, Cheema MS, Clarke R.Application of metabolomics in drug resistant breast cancer research.Metabolites. 2015; 5(1): 100-118.
6 Xu J, Wang Y, Xu DS, Ruan KF, Feng Y, Wang S.Hypoglycemic effects of MDG-1, a polysaccharide derived fromOphiopogon japonicas, in the ob/ob mouse model of type 2 diabetes mellitus. Int J Biol Macromol. 2011; 49(4): 657-662.
7 Lin X, Lu Z, Xu D, Feng Y, Shen L. Oral absorption enhancers of Ophiopogon japonicas polysaccharides. Zhongguo Zhong Yao Za Zhi.2009; 34(12): 1498-1502. Chinese with abstract in English.
8 Lin X, Lu Z, Xu D, Feng Y. Comparison of distribution of Ophiopogon japonicas polysaccharide in hearts of normal rats and myocardial ischemic rats. Zhongguo Zhong Yao Za Zhi.2009; 34(2): 230-233. Chinese with abstract in English.
9 Chen YT, Yuan Q, Shan LT, Lin MA, Cheng DQ, Li CY.Antitumor activity of bacterial exopolysaccharides from the endophyteBacillus amyloliquefaciens sp. isolated from Ophiopogon japonicus. Oncol Lett. 2013; 5(6): 1787-1792.
10 Chen M, Yang ZW, Zhu JT, Xiao ZY, Xiao R. Anti-arrhythmic effects and electrophysiological properties of Ophiopogon total saponins. Zhongguo Yao Li Xue Bao.1990; 11(2): 161-165. Chinese with abstract in English.
11 Sun K, Cao S, Pei L, Matsuura A, Xiang L, Qi J.A steroidal saponin fromOphiopogon japonicus extends the lifespan of yeast via the pathway involved in SOD and UTH1. Int J Mol Sci. 2013; 14(3): 4461-4475.
12 Liang H, Xing Y, Chen J, Zhang D, Guo S, Wang C.Antimicrobial activities of endophytic fungi isolated fromOphiopogon japonicus (Liliaceae). BMC Complement Altern Med. 2012; 12: 238.
13 Chen M, Du Y, Qui M, Wang M, Chen K, Huang Z, Jiang M, Xiong F, Chen J, Zhou J, Jiang F, Yin L, Tang Y, Ye L, Zhan Z, Duan J, Fu H, Zhang X.Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway.Oncol Rep. 2013; 29(2): 430-436.
14 Kou J, Tian Y, Tang Y, Yan J, Yu B.Antithrombotic activities of aqueous extract from Radix Ophiopogon japonicus and its two constituents. Biol Pharm Bull. 2006; 29(6): 1267-1270.
15 Kou J, Sun Y, Lin Y, Cheng Z, Zheng W, Yu B, Xu Q.Anti-inflammatory activities of aqueous extract fromRadix Ophiopogon japonicus and its two constituents. Biol Pharm Bull. 2005; 28(7): 1234-1238.
16 Gao N, Cheng S, Budhraja A, Liu EH, Chen J, Chen D, Yang Z, Luo J, Shi X, Zhang Z.3,3′-Diindolylmethane exhibits antileukemic activityin vitro and in vivo through a Akt-dependent process. PLoS One. 2012; 7(2): e31783.
17 Huang C, Gu S, Yu P, Yu F, Feng C, Gao N, Du J.Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities in zebrafish.Dev Biol. 2010; 339(1): 89-100.
18 Zhang J, Zhu X, Li H, Li B, Sun L, Xie T, Zhu T, Zhou H, Ye Z.Piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression.Int Immunopharmacol. 2014; 24(1): 50-58.
19 Zeng QY, Zeng LJ, Huang Y, Huang YQ, Zhu QF, Liao ZH.8-60hIPP5(m)-induced G2/M cell cycle arrest involves activation of ATM/p53/p21(cip1/waf1) pathways and delayed cyclin B1 nuclear translocation.Asian Pac J Cancer Prev. 2014; 15(9): 4101-4107.
20 Lim S, Kaldis P.Cdks, cyclins and CKIs: roles beyond cell cycle regulation.Development. 2013; 140(15): 3079-3093.
21 Lange C, Calegari F.Cdks and cyclins link G1 length and differentiation of embryonic, neural and hematopoietic stem cells.Cell Cycle. 2010; 9(10): 1893-1900.
22 Marais A, Ji Z, Child ES, Krause E, Mann DJ, Sharrocks AD.Cell cycle-dependent regulation of the forkhead transcription factor FOXK2 by CDK·cyclin complexes.J Biol Chem. 2010; 285(46): 35728-35739.
23 Hasegawa H, Ishibashi K, Kubota S, Yamaguchi C, Yuki R, Nakajo H, Eckner R, Yamaguchi N, Yokoyama KK.Cdk1- mediated phosphorylation of human ATF7 at Thr-51 and Thr-53 promotes cell-cycle progression into M phase.PLoS One. 2014; 9(12): e116048.
24 Creagh EM.Caspase crosstalk: integration of apoptotic and innate immune signalling pathways.Trends Immunol. 2014; 35(12): 631-640.
25 Liu LH, Zhang M. Caspase-independent programmed cell death induced by temozolomide in rat glioma C6 cell line. Nan Fang Yi Ke Da Xue Xue Bao.2015; 35(2): 229-233. Chinese with abstract in English.
26 Busbee PB, Nagarkatti M, Nagarkatti PS.Natural indoles, indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM), attenuate staphylococcal enterotoxin B-mediated liver injury by downregulating miR-31 expression and promoting caspase- 2-mediated apoptosis.PLoS One. 2015; 10(2): e0118506.
27 Yang HJ, Wang M, Wang L, Cheng BF, Lin XY, Feng ZW.NF-κB regulates caspase-4 expression and sensitizes neuroblastoma cells to Fas-induced apoptosis.PLoS One. 2015; 10(2): e0117953.
28 Lee WS, Yun JW, Nagappan A, Jung JH, Yi SM, Kim DH, Kim HJ, Kim G, Ryu CH, Shin SC, Hong SC, Choi YH, Jung JM.Flavonoids fromOrostachys Japonicus A. Berger induces caspase-dependent apoptosis at least partly through activation of p38 MAPK pathway in U937 human leukemic cells. Asian Pac J Cancer Prev. 2015; 16(2): 465-469.
29 Baharara J, Namvar F, Ramezani T, Mousavi M, Mohamad R.Silver nanoparticles biosynthesized usingAchillea biebersteinii flower extract: apoptosis induction in MCF-7 cells via caspase activation and regulation of Bax and Bcl-2 gene expression. Molecules. 2015; 20(2): 2693-2706.
30 Chaabane W, Cieslar-Pobuda A, El-Gazzah M, Jain MV, Rzeszowska-Wolny J, Rafat M, Stetefeld J, Ghavami S, Los MJ.Human-gyrovirus-apoptin triggers mitochondrial death pathway — Nur77 is required for apoptosis triggering.Neoplasia. 2014; 16(9): 679-693.
31 Chou YC, Chang MY, Wang MJ, Harnod T, Hung CH, Lee HT, Shen CC, Chung JG.PEITC induces apoptosis of human brain glioblastoma GBM8401 cells through the extrinsic-and intrinsic-signaling pathways.Neurochem Int. 2015; 81: 32-40.
32 Fang C, Zhang J, Qi D, Fan X, Luo J, Liu L, Tan Q.Evodiamine induces G2/M arrest and apoptosis via mitochondrial and endoplasmic reticulum pathways in H446 and H1688 human small-cell lung cancer cells. PLoS One. 2014; 9(12): e115204.

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Ophiopogonin D inhibits cell proliferation, causes cell cycle arrest at G₂/M, and induces apoptosis in human breast carcinoma MCF-7 cells

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