Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP.

BioMed Research International
Zhuan-Li BaiMao-Guo Shu

Abstract

Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum. Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners. Meanwhile, silibinin induced autophagy through upregulation of microtubule-associated protein a light chain 3- (LC3-) II. And autophagy inhibition with chloroquine, a lysosomotropic agent, significantly enhanced silibinin induced glioblastoma cell apoptosis. Moreover, silibinin dose-dependently downregulated the phosphorylation levels of mTOR at Ser-2448, p70S6K at Thr-389, and 4E-BP1 at Thr-37/46. Furthermore, the expression of YAP, the downstream effector of Hippo signal pathway, was also suppressed by silibinin. These r...Continue Reading

References

Dec 12, 2001·Drugs·R SallerR Brignoli
Aug 9, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Rana P Singh, Rajesh Agarwal
Nov 17, 2007·Genes & Development·Noboru Mizushima
Oct 17, 2009·Journal of Pharmacological Sciences·Yuan-yuan JiangTakashi Ikejima
Apr 8, 2010·Free Radical Research·Hong-Jun WangTakashi Ikejima
Aug 18, 2010·Cancer Metastasis Reviews·Gagan Deep, Rajesh Agarwal
Oct 23, 2010·Molecular Cell·Guido KroemerBeth Levine
Mar 25, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Harel DahariAlan S Perelson
Apr 24, 2013·Journal of Photochemistry and Photobiology. B, Biology·Weiwei LiuTakashi Ikejima
May 14, 2014·Free Radical Biology & Medicine·Gaetano ServiddioAnna Maria Giudetti
Jul 24, 2014·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Jigisha P ThakkarJohn L Villano
Oct 8, 2014·The Journal of Experimental Medicine·Ning LiangMario Pende
Oct 22, 2014·Immunology and Cell Biology·Donna DentonSharad Kumar
Sep 27, 2016·Clinical Journal of Oncology Nursing·Mary Elizabeth Davis
Oct 28, 2016·Cell Death & Disease·Soha JawhariMireille Verdier
Dec 6, 2016·Critical Reviews in Oncogenesis·Janis NoonanBrona M Murphy
Jan 27, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alessandro FedericoCarmelina Loguercio
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Joachim BischofTimo Burster
May 4, 2017·Biological Reviews of the Cambridge Philosophical Society·Juan LorenteMatilde E LLeonart
May 4, 2017·Cell Metabolism·Alec C Kimmelman, Eileen White

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Citations

Nov 14, 2019·Current Drug Delivery·Milad AshrafizadehSaeed Samarghandian
Feb 1, 2020·Current Pharmaceutical Design·Seyed Hossein ShahcheraghiHamid Reza Sadeghnia
Oct 30, 2018·BioMed Research International·Flávio Fernandes Veloso BorgesLee Chen-Chen
Feb 2, 2021·Oncotarget·Gina Abdelaal, Stephany Veuger
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shalini Sundramurthi ChelliahIshwar Parhar
Oct 14, 2020·Journal of Agricultural and Food Chemistry·Xin WangShuai-Cheng Wu
Nov 6, 2021·Cellular and Molecular Gastroenterology and Hepatology·Shuyi ChenXiuling Zhi

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