title: Autophagy inhibition enhances silibinin-induced apoptosis by regulating reactive oxygen species production in human prostate cancer PC-3 cells.
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.
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea.
authors.forename: Kwang-Youn
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Sun-Nyoung
authors.initials: SN
authors.lastname: Yu
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Hyeun-Deok
authors.initials: HD
authors.lastname: Choi
authors.affiliation: Genome Instability Research, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Ji
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea. Electronic address: ahnsc@pusan.ac.kr.
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020944:Silybum marianum / Q000737:chemistry; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D012838:Silymarin; D000077385:Silybin
keywords: Apoptosis; Autophagy; PC-3 cells; Reactive oxygen species; Silibinin