Autophagy inhibition enhances silibinin-induced apoptosis by regulating reactive oxygen species production in human prostate cancer PC-3 cells

Biochem Biophys Res Commun. 2015 Dec;468(1-2):151-6. doi: 10.1016/j.bbrc.2015.10.143. Epub 2015 Oct 30.

Abstract

Silibinin is a major bioactive component of silymarin and has anticancer effects on cancer cell line and has been used as a supportive therapy for chronic inflammatory liver condition. These anticancer effects of silibinin have been demonstrated both in vitro and in vivo cancer models. Although various evidences showed apoptosis signaling pathways by silibinin, there is no report to address the clearly mechanism of silibinin-induced autophagy in prostate cancer PC-3 cells. Our study showed that silibinin triggered autophagy through up-regulation of microtubule-associated protein 1 light chain 3 (LC3)-II, formation of acidic vesicular organelles (AVO) and punctuate of GFP-LC3, which was inhibited by 3-methyladenine (3-MA), an inhibitor of specific autophagy. In addition, silibinin induced autophagy through production of reactive oxygen species (ROS). Inhibition of ROS with diphenyleneiodonium (DPI), a ROS inhibitor, attenuated silibinin-triggered autophagy. Inhibition of autophagy with 3-MA enhanced the silibinin-induced apoptosis through the regulation of caspase-3 and PARP. These results suggested that silibinin induced autophagy by regulating ROS and its mechanism played a protective role against apoptosis in PC-3 cells.

Keywords: Apoptosis; Autophagy; PC-3 cells; Reactive oxygen species; Silibinin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Humans
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Reactive Oxygen Species / metabolism*
  • Silybin
  • Silybum marianum / chemistry
  • Silymarin / pharmacology*

Substances

  • Antioxidants
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • Silymarin
  • Silybin