title: Nitric oxide (•NO) generation but not ROS plays a major role in silibinin-induced autophagic and apoptotic death in human epidermoid carcinoma A431 cells.
abstract: Silibinin, a major active constituent of silymarin, is clinically used as a hepatoprotectant, and in recent years, it has been used for the treatment of cancer in China. Because the mechanism of silibinin action on cancer cells was still unclear, we investigated the contribution of silibinin to the induction of apoptosis and autophagy via generation of reactive oxygen species (ROS) and nitric oxide (•NO) in human epidermoid carcinoma A431 cells. Silibinin inhibited the cell growth in a dose-and time-dependent manner. Obvious autophagy was observed after treatment with different doses of silibinin. At a high dose (400 μM), silibinin induced apoptosis through both the intrinsic and extrinsic apoptotic pathways. Loss of mitochondrial membrane potential by silibinin led to mitochondrial dysfunction and decreased ROS levels, suggesting that silibinin might act as an antioxidant in this process. Furthermore, silibinin induced •NO generation in a time-and dose-dependent manner. The •NO scavenger PTIO could effectively clear •NO and exerted a minor cell protection effect through partial inhibition of silibinin-induced apoptosis and autophagy.
authors.affiliation: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Si Miao
authors.initials: SM
authors.lastname: Fan
authors.forename: Su Juan
authors.initials: SJ
authors.lastname: Yuan
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: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D000077385:Silybin; D012838:Silymarin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D005609:Free Radicals; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D012838:Silymarin; D009569:Nitric Oxide; D000077385:Silybin