Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan.
J Biochem Mol Toxicol. 2012 Nov;26(11):445-53. doi: 10.1002/jbt.21443. Epub 2012 Nov 5.
Anthocyanidins, which are polyphenols that are believed to be effective for preventing cancer, are composed of a basic structure of the plant pigment anthocyanin. In this study, we investigated the biological activity of anthocyanidins, including delphinidin, against HeLa cells. The cytotoxicity observed in the anthocyanidins-treated cells was well correlated with the inhibitory effects of anthocyanidins on c-Jun-dependent transcriptional activity. Remarkably, anthocyanidin induced autophagosome formation but lacked the ability to induce apoptosis. Notably, delphinidin enhanced autolysosome formation as well as autophagosome formation. Delphinidin treatment resulted in the accumulation of the lipidated form of Map1lc3b protein in an Atg5-dependent manner in mouse embryonic fibroblasts. Finally, we revealed that the cytotoxicity induced by delphinidin was more severe in Atg5-deficient mouse embryonic fibroblasts than in wild-type cells. Taken together, these results indicate that the cytotoxicity induced by delphinidin was accompanied by autophagy and delphinidin-induced autophagy exerted a cell protective role.
花色苷，是一种被认为具有预防癌症功效的多酚类化合物，由植物色素花色苷的基本结构组成。在这项研究中，我们研究了花色苷（包括飞燕草素）对 HeLa 细胞的生物活性。花色苷处理细胞后的细胞毒性与花色苷对 c-Jun 依赖性转录活性的抑制作用密切相关。值得注意的是，花色苷诱导自噬体形成，但缺乏诱导细胞凋亡的能力。飞燕草素能够显著增强自噬体和自溶酶体的形成。在小鼠胚胎成纤维细胞中，飞燕草素处理导致 Map1lc3b 蛋白的脂化形式积累，这种积累依赖于 Atg5。最后，我们揭示了在 Atg5 缺失型的小鼠胚胎成纤维细胞中，与野生型细胞相比，飞燕草素诱导的细胞毒性更为严重。综上所述，这些结果表明，飞燕草素诱导的细胞毒性伴随着自噬作用，而飞燕草素诱导的自噬起到了细胞保护作用。
