1. Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis
- Author
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Liu, Weiwei, Otkur, Wuxiyar, Li, Lingzhi, Wang, Qiong, He, Hao, Zang, Linghe, Hayashi, Toshihiko, Tashiro, Shin-ichi, Onodera, Satoshi, Xia, Mingyu, and Ikejima, Takashi
- Subjects
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SILIBININ , *INSULIN-like growth factor receptors , *SKIN cancer , *CELLULAR signal transduction , *APOPTOSIS , *ULTRAVIOLET radiation , *PRECANCEROUS conditions - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2013
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