Abstract
We previously reported that silibinin induced a loss of cell viability in breast cancer (MCF-7) cells by ERα down-regulation. But whether this cytotoxicity depends on another estrogen receptor, ERβ, has yet to be elucidated. Therefore, we sought to explore the effects of ERβ modulation on cell viability by using an ERβ-selective agonist (Diarylprepionitrile, DPN) and an antagonist (PHTPP). Our data demonstrated that ERβ served as a growth suppressor in MCF-7 cells, and the incubation of silibinin, elevated ERβ expression, resulting in the tumor growth inhibition. The cytotoxic effect of silibinin was diminished by PHTPP and enhanced by DPN. Silencing of ERβ by siRNA confirmed these results. Apoptotic cascades, including the sequential activation of caspase-9 and -6, and finally the cleavage of caspase substrates, PARP and ICAD, caused by treatment with silibinin, were all repressed by PHTPP pre-treatment but exacerbated by DPN. Unlike ERα, ERβ did not involve autophagic process in the regulation, since neither autophagic inhibitor (3-MA) nor the inducer (rapamycin) affected the cell survival rates regardless ERβ activity. Taken together, silibinin induced apoptosis through mitochondrial pathway by up-regulating ERβ pathways in ...Continue Reading
References
Dec 9, 1997·Cell·P LiX Wang
Nov 16, 2001·Journal of Medicinal Chemistry·M J MeyersJ A Katzenellenbogen
Jun 1, 2002·Science·Harald Wajant
Jan 23, 2004·American Journal of Physiology. Endocrinology and Metabolism·Jin Q ChenJames D Yager
Aug 25, 2004·The International Journal of Biochemistry & Cell Biology·Noboru Mizushima
Nov 13, 2004·Journal of Medicinal Chemistry·Dennis R ComptonJohn A Katzenellenbogen
Nov 17, 2004·IUBMB Life·Pierangela TottaMaria Marino
Sep 24, 2005·Cell·Sophie PattingreBeth Levine
Dec 13, 2005·Endocrinology·Filippo AcconciaRakesh Kumar
Apr 14, 2006·Current Medicinal Chemistry·Fernando A Crocenzi, Marcelo G Roma
Jun 24, 2006·Cell Death and Differentiation·Y KourokuT Momoi
Apr 5, 2007·Nature Protocols·Carlo Riccardi, Ildo Nicoletti
Dec 18, 2007·Cell·Masaaki KomatsuKeiji Tanaka
Jul 23, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ana M Covaleda SotocaAlbertinka J Murk
Feb 3, 2009·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Sangmin KimJeong Eon Lee
Apr 25, 2012·Cytotechnology·Kazem Nejati-KoshkiHamid Tayefi-Nasrabadi
Oct 23, 2012·Biophysical Chemistry·Sandipan ChakrabortyP K Biswas
Jan 30, 2014·The Journal of Pharmacology and Experimental Therapeutics·Thae Hyun KimKi Hyung Kim
Dec 11, 2014·World Journal of Clinical Oncology·Andrea MilaniGiorgio Valabrega
Aug 16, 2015·Biochemical Pharmacology·Joung Hyuck JooAnton M Jetten
Citations
Jul 1, 2016·Expert Review of Clinical Pharmacology·Xing-Xing ZhuQiang He
Nov 22, 2016·Acta Pharmacologica Sinica·Nan ZhengTakashi Ikejima
Feb 6, 2018·Neurochemical Research·Xiaoyu SongTakashi Ikejima
Apr 6, 2019·Free Radical Research·Yang YuCheng Xu
Sep 4, 2018·Frontiers in Immunology·Maria Luisa DupuisMarina Pierdominici
Jun 29, 2018·International Journal of Molecular Sciences·Deisi L BragaThaise G Araújo
Sep 19, 2020·Biomarker Research·Yujing Zhou, Xingdang Liu
Oct 6, 2017·Pathogens and Disease·Yuanbin SunLili Chen
Dec 6, 2020·Biochimie·Cristina Ferreira AlmeidaCristina Amaral
Feb 10, 2021·Journal of Photochemistry and Photobiology. B, Biology·Weiwei LiuTakashi Ikejima
Dec 21, 2019·Anti-cancer Agents in Medicinal Chemistry·Agata BiniendaElzbieta Pluciennik
Nov 2, 2020·Seminars in Cancer Biology·Hardeep Singh TuliAnil Kumar Sharma
Mar 24, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jing YangTakashi Ikejima