title: Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis.
abstract: Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation. The activation of the IGF-1R signalling pathways contributed to apoptosis of the cells rather than rescuing the cells from death. Up-regulated IGF-1R stimulated downstream mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). The subsequent activation of caspase-8 and caspase-3 led to apoptosis. The activation of IGF-1R signalling pathways is the cause of A431 cell death. The pharmacological inhibitors and the small interfering RNA (siRNA) targeting IGF-1R suppressed the downstream activation of JNK/ERK-caspases to help the survival of the UVB-irradiated A431 cells. Indeed, silibinin treatment suppressed the IGF-1R-JNK/ERK pathways and thus protected the cells from UVB-induced apoptosis.
authors: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Weiwei
authors: W
authors: Liu
authors: Wuxiyar
authors: W
authors: Otkur
authors: Lingzhi
authors: L
authors: Li
authors: Qiong
authors: Q
authors: Wang
authors: Hao
authors: H
authors: He
authors: Linghe
authors: L
authors: Zang
authors: Toshihiko
authors: T
authors: Hayashi
authors: Shin-ichi
authors: S
authors: Tashiro
authors: Satoshi
authors: S
authors: Onodera
authors: Mingyu
authors: M
authors: Xia
authors: Takashi
authors: T
authors: Ikejima
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004789:Enzyme Activation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D012838:Silymarin; D000077385:Silybin; D017526:Receptor, IGF Type 1; D053181:Caspase 8; D053453:Caspase 9