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水飞蓟素对紫外线诱导的A375-S2细胞凋亡的保护作用涉及SIRT1信号通路的激活和细胞周期的调节。

Activation of the SIRT1 pathway and modulation of the cell cycle were involved in silymarin's protection against UV-induced A375-S2 cell apoptosis.

作者信息

Li L-H, Wu L-J, Tashiro S-I, Onodera S, Uchiumi F, Ikejima T

机构信息

China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.

出版信息

J Asian Nat Prod Res. 2007 Apr-Aug;9(3-5):245-52. doi: 10.1080/10286020600604260.

DOI:10.1080/10286020600604260
PMID:17566917
Abstract

Silymarin, derived from the milk thistle plant, Silybum marianum, has been traditionally used in the treatment of liver disease. Our previous study demonstrated that silymarin has an anti-apoptotic effect against UV irradiation. In this study, SIRT1, a human deacetylase that was reported to promote cell survival, was activated by silymarin (5 x 10(- 4) mol/L) in UV-irradiated human malignant melanoma, A375-S2 cells, followed by down-regulated expression of Bax and decreased release of cytochrome c. Cleavage of procaspase-3 and digestion of its substrates, the inhibitor of caspase-activated DNase (ICAD) and poly(ADP-ribose) polymerase (PARP), were also reduced. Consistent with its protective effect on UV-induced apoptosis, silymarin (5 x 10(- 4) mol/L) also increased G(2)/M phase arrest, possibly providing a prolonged time for efficient DNA repair. Consequently, that silymarin protected A375-S2 cell against UV-induced apoptosis was partially through SIRT1 pathway and modulation of the cell cycle distribution.

摘要

水飞蓟素源自水飞蓟属植物水飞蓟,传统上用于治疗肝脏疾病。我们之前的研究表明,水飞蓟素对紫外线照射具有抗凋亡作用。在本研究中,据报道可促进细胞存活的人类去乙酰化酶SIRT1在紫外线照射的人类恶性黑色素瘤A375 - S2细胞中被水飞蓟素(5×10⁻⁴ mol/L)激活,随后Bax表达下调,细胞色素c释放减少。procaspase - 3的切割及其底物——半胱天冬酶激活的DNA酶抑制剂(ICAD)和聚(ADP - 核糖)聚合酶(PARP)的消化也减少。与其对紫外线诱导凋亡的保护作用一致,水飞蓟素(5×10⁻⁴ mol/L)还增加了G₂/M期阻滞,可能为有效的DNA修复提供了更长时间。因此,水飞蓟素保护A375 - S2细胞免受紫外线诱导凋亡部分是通过SIRT1途径和细胞周期分布的调节实现的。

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