title: Autophagy induced by silibinin protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis.
abstract: Ultraviolet B (UVB) in the sun light is a major cause of skin damage, which accompanies complex alterations in irradiated skin cells, including DNA lesions, oxidative stress, inflammation and caspase activation. The protection against UVB damage requires multiple interruptions such as repair of the DNA lesions, scavenging of the reactive oxygen species (ROS), repression of the inflammation and others. Silibinin is suggested as an anti-UVB reagent, but the underlying mechanisms have not been fully elucidated. In this study, we found a role of autophagy in the anti-UVB effect of silibinin in A431 cells. Autophagy was reduced after UVB-irradiation while restored by silibinin through the suppression of the IGF-1R signalling pathway. The protective effect of silibinin in UVB-irradiated A431 cells was further enhanced by pre-treatment with an autophagy inducer, rapamycin, while it was reversed by an autophagy inhibitor, wortmannin, indicating that elevated autophagy contributed to the cell survival. Consistently, cell apoptosis was augmented by siRNAs targeting Beclin 1 and Atg5, supporting the hypothesis that autophagy induced by silibinin plays a protective role against UVB-induced epidermal apoptosis.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.forename: Wuxiyar
authors.initials: W
authors.lastname: Otkur
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Ye
authors.forename: Yuning
authors.initials: Y
authors.lastname: Zhang
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Onodera
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors; D001343:Autophagy / Q000187:drug effects* / Q000528:radiation effects; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000502:physiology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D000077191:Wortmannin
chemical_list: C502778:ATG5 protein, human; D000730:Androstadienes; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D012838:Silymarin; D000077385:Silybin; D017526:Receptor, IGF Type 1; D020123:Sirolimus; D000077191:Wortmannin