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Different apoptotic effects of saxifragifolin C in human breast cancer cells

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A Correction to this article was published on 22 November 2018

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Abstract

Breast cancer is currently the most common form of cancer affecting women. Recent studies have reported that triterpenoid saponins isolated from Androsace umbellata exhibit anti-proliferative effects in several types of cancer cells. However, the cytotoxic effect of saxifragifolin C (Saxi C) on breast cancer cells remains unclear. The purpose of this study is to evaluate the in vitro anti-tumor activity of Saxi C in human breast cancer cells. Our data indicated that MDA-MB-231 cells were more sensitive than MCF-7 cells to Saxi C treatment. In addition, Saxi C inhibited cell survival through the induction of reactive oxygen species and the caspase-dependent pathway in the MDA-MB-231 cells, whereas MCF-7 cells treated with Saxi C underwent the apoptotic cell death in a caspase-independent manner. Although Saxi C treatment resulted in the induction of activation of MAPKs in both types of human breast cancer cells, p38 MAPK and JNK, but not ERK1/2, appeared to be involved in Saxi C-induced apoptosis. Moreover, ERα-overexpressing MDA-MB-231 cells remained alive, whereas the survival of shERα-transfected MCF-7 cells decreased. Taken together, Saxi C induced apoptosis in MCF-7 cells and MDA-MB-231 cells via different regulatory mechanisms, and ERα status might be essential for regulating Saxi C-induced apoptosis in breast cancer cells. Thus, Saxi C is a potential chemotherapeutic agent in breast cancer.

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Change history

  • 22 November 2018

    The authors regret that incorrect western band of Bax (MDA-MB-231) in Fig. 6a (right panel) was mistakenly uploaded in the original publication. The correct Fig. 6a is shown below. This correction does not change the conclusions of this manuscript. The authors would like to apologize for any inconvenience caused.

  • 22 November 2018

    The authors regret that incorrect western band of Bax (MDA-MB-231) in Fig.��6a (right panel) was mistakenly uploaded in the original publication. The correct Fig.��6a is shown below. This correction does not change the conclusions of this manuscript. The authors would like to apologize for any inconvenience caused.

References

  • Arnoult D, Parone P, Martinou JC, Antonsson B, Estaquier J, Ameisen JC (2002) Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli. J Cell Biol 159(6):923–929

    Article  CAS  Google Scholar 

  • Bishayee A, Ahmed S, Brankov N, Perloff M (2011) Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front Biosci 16:980–996

    Article  CAS  Google Scholar 

  • Brower V (2008) Back to nature: extinction of medicinal plants threatens drug discovery. J Natl Cancer Inst 100(12):838–839

    Article  Google Scholar 

  • Chan SL, Yu VC (2004) Proteins of the bcl-2 family in apoptosis signalling: from mechanistic insights to therapeutic opportunities. Clin Exp Pharmacol Physiol 31(3):119–128

    Article  CAS  Google Scholar 

  • Chen CH, deGraffenried LA (2012) Anethole suppressed cell survival and induced apoptosis in human breast cancer cells independent of estrogen receptor status. Phytomedicine 19(8–9):763–767

    Article  CAS  Google Scholar 

  • Chung H, Jung YM, Shin DH, Lee JY, Oh MY, Kim HJ, Jang KS, Jeon SJ, Son KH, Kong G (2008) Anticancer effects of wogonin in both estrogen receptor-positive and -negative human breast cancer cell lines in vitro and in nude mice xenografts. Int J Cancer 122(4):816–822

    Article  CAS  Google Scholar 

  • Cook KL, Clarke PA, Parmar J, Hu R, Schwartz-Roberts JL, Abu-Asab M, Warri A, Baumann WT, Clarke R (2014) Knockdown of estrogen receptor-alpha induces autophagy and inhibits antiestrogen-mediated unfolded protein response activation, promoting ROS-induced breast cancer cell death. FASEB J 28(9):3891–3905

    Article  CAS  Google Scholar 

  • Dalmau E, Armengol-Alonso A, Munoz M, Segui-Palmer MA (2014) Current status of hormone therapy in patients with hormone receptor positive (HR +) advanced breast cancer. Breast 23(6):710–720

    Article  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35(4):495–516

    Article  CAS  Google Scholar 

  • Elumalai P, Arunkumar R, Benson CS, Sharmila G, Arunakaran J (2014) Nimbolide inhibits IGF-I-mediated PI3K/Akt and MAPK signalling in human breast cancer cell lines (MCF-7 and MDA-MB-231). Cell Biochem Funct 32(5):476–484

    CAS  PubMed  Google Scholar 

  • Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281(5381):1309–1312

    Article  CAS  Google Scholar 

  • Hatano E, Bradham CA, Stark A, Iimuro Y, Lemasters JJ, Brenner DA (2000) The mitochondrial permeability transition augments Fas-induced apoptosis in mouse hepatocytes. J Biol Chem 275(16):11814–11823

    Article  CAS  Google Scholar 

  • He Z, Chen H, Li G, Zhu H, Gao Y, Zhang L, Sun J (2014) Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity. Phytomedicine 21(6):871–876

    Article  CAS  Google Scholar 

  • Herrera B, Alvarez AM, Sanchez A, Fernandez M, Roncero C, Benito M, Fabregat I (2001) Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor (beta) in fetal hepatocytes. FASEB J 15(3):741–751

    Article  CAS  Google Scholar 

  • Ijichi N, Shigekawa T, Ikeda K, Horie-Inoue K, Fujimura T, Tsuda H, Osaki A, Saeki T, Inoue S (2011) Estrogen-related receptor gamma modulates cell proliferation and estrogen signaling in breast cancer. J Steroid Biochem Mol Biol 123(1–2):1–7

    Article  CAS  Google Scholar 

  • Im JY, Park H, Kang KW, Choi WS, Kim HS (2008) Modulation of cell cycles and apoptosis by apicidin in estrogen receptor (ER)-positive and-negative human breast cancer cells. Chem Biol Interact 172(3):235–244

    Article  CAS  Google Scholar 

  • Janicke RU (2009) MCF-7 breast carcinoma cells do not express caspase-3. Breast Cancer Res Treat 117(1):219–221

    Article  Google Scholar 

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  Google Scholar 

  • Kim HJ, Cho SD, Kim J, Kim SJ, Choi C, Kim JS, Nam JS, Han Kwon K, Kang KS, Jung JY (2013) Apoptotic effect of tolfenamic acid on MDA-MB-231 breast cancer cells and xenograft tumors. J Clin Biochem Nutr 53(1):21–26

    Article  CAS  Google Scholar 

  • Li JW, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325(5937):161–165

    Article  Google Scholar 

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91(4):479–489

    Article  CAS  Google Scholar 

  • Li X, Wang K, Ren Y, Zhang L, Tang XJ, Zhang HM, Zhao CQ, Liu PJ, Zhang JM, He JJ (2014) MAPK signaling mediates sinomenine hydrochloride-induced human breast cancer cell death via both reactive oxygen species-dependent and -independent pathways: an in vitro and in vivo study. Cell Death Dis 5:e1356

    Article  CAS  Google Scholar 

  • Lin Y, Jiang D, Li Y, Han X, Yu D, Park JH, Jin YH (2015) Effect of sun ginseng potentiation on epirubicin and paclitaxel-induced apoptosis in human cervical cancer cells. J Ginseng Res 39(1):22–28

    Article  Google Scholar 

  • Mohamed A, Krajewski K, Cakar B, Ma CX (2013) Targeted therapy for breast cancer. Am J Pathol 183(4):1096–1112

    Article  CAS  Google Scholar 

  • Nishino H, Nishino A, Takayasu J, Hasegawa T, Iwashima A, Hirabayashi K, Iwata S, Shibata S (1988) Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleanane-type triterpenoid compounds. Cancer Res 48(18):5210–5215

    CAS  PubMed  Google Scholar 

  • Park JH, Kwak JH, Khoo JH, Park SH, Kim DU, Ha DM, Choi SU, Kang SC, Zee OP (2010) Cytotoxic effects of triterpenoid saponins from Androsace umbellata against multidrug resistance (MDR) and non-MDR cells. Arch Pharm Res 33(8):1175–1180

    Article  CAS  Google Scholar 

  • Park DH, De Xu H, Shim J, Li YC, Lee JH, Cho SC, Han SS, Lee YL, Lee MJ, Kwon SW (2011) Stephania delavayi Diels. inhibits breast carcinoma proliferation through the p38 MAPK/NF-kappaB/COX-2 pathway. Oncol Rep 26(4):833–841

    PubMed  Google Scholar 

  • Rabi T, Banerjee S (2008) Novel synthetic triterpenoid methyl 25-hydroxy-3-oxoolean-12-en-28-oate induces apoptosis through JNK and p38 MAPK pathways in human breast adenocarcinoma MCF-7 cells. Mol Carcinog 47(6):415–423

    Article  CAS  Google Scholar 

  • Rochefort H, Glondu M, Sahla ME, Platet N, Garcia M (2003) How to target estrogen receptor-negative breast cancer? Endocr Relat Cancer 10(2):261–266

    Article  CAS  Google Scholar 

  • Santha S, Bommareddy A, Rule B, Guillermo R, Kaushik RS, Young A, Dwivedi C (2013) Antineoplastic effects of alpha-santalol on estrogen receptor-positive and estrogen receptor-negative breast cancer cells through cell cycle arrest at G2/M phase and induction of apoptosis. PLoS ONE 8(2):e56982

    Article  CAS  Google Scholar 

  • Shi JM, Bai LL, Zhang DM, Yiu A, Yin ZQ, Han WL, Liu JS, Li Y, Fu DY, Ye WC (2013) Saxifragifolin D induces the interplay between apoptosis and autophagy in breast cancer cells through ROS-dependent endoplasmic reticulum stress. Biochem Pharmacol 85(7):913–926

    Article  CAS  Google Scholar 

  • Sledge GW Jr (2004) Breast cancer as a world challenge. Clin Breast Cancer 5(1):11

    Article  Google Scholar 

  • Sreeja S, Santhosh Kumar TR, Lakshmi BS, Sreeja S (2012) Pomegranate extract demonstrate a selective estrogen receptor modulator profile in human tumor cell lines and in vivo models of estrogen deprivation. J Nutr Biochem 23(7):725–732

    Article  CAS  Google Scholar 

  • Su B, Karin M (1996) Mitogen-activated protein kinase cascades and regulation of gene expression. Curr Opin Immunol 8(3):402–411

    Article  CAS  Google Scholar 

  • Wang C, Youle RJ (2009) The role of mitochondria in apoptosis. Annu Rev Genet 43:95–118

    Article  CAS  Google Scholar 

  • Wang Y, Zhang D, Ye W, Yin Z, Fung KP, Zhao S, Yao X (2008) Triterpenoid saponins from Androsace umbellata and their anti-proliferative activities in human hepatoma cells. Planta Med 74(10):1280–1284

    Article  CAS  Google Scholar 

  • Won YS, Lee JH, Kwon SJ, Kim JY, Park KH, Lee MK, Seo KI (2014) alpha-Mangostin-induced apoptosis is mediated by estrogen receptor alpha in human breast cancer cells. Food Chem Toxicol 66:158–165

    Article  CAS  Google Scholar 

  • Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9(1):47–59

    Article  CAS  Google Scholar 

  • Zhang DM, Wang Y, Tang MK, Chan YW, Lam HM, Ye WC, Fung KP (2007) Saxifragifolin B from Androsace umbellata induced apoptosis on human hepatoma cells. Biochem Biophys Res Commun 362(3):759–765

    Article  CAS  Google Scholar 

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    Authors and Affiliations

    1. School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea

      Kyung-Ho Kim, Ji-Yun Kim, Jong-Hwan Kwak & Suhkneung Pyo

    2. School of Food Science & Biotechnology, College of Agriculture & Life Sciences, Kyungpook National University, Daegu, Republic of Korea

      Byung Oh Kim

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    Kyung-Ho Kim and Ji-Yun Kim equally contributed to this work.

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    Kim, KH., Kim, JY., Kwak, JH. et al. Different apoptotic effects of saxifragifolin C in human breast cancer cells. Arch. Pharm. Res. 39, 577–589 (2016). https://doi.org/10.1007/s12272-016-0729-5

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