Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.
J Photochem Photobiol B. 2019 May;194:84-95. doi: 10.1016/j.jphotobiol.2019.03.010. Epub 2019 Mar 21.
Ultraviolet (UV)-B radiation is a major environmental risk factor that is responsible for the development and progression of many skin cancers. Apigenin, a type of bioflavonoid, has been reported to inhibit UVB-induced skin cancer. However, how apigenin functions in keratinocytes with UV damage remains unclear. In this study, by lactate dehydrogenase (LDH) release assay, we found that apigenin treatment increased cell death in the primary human epidermal keratinocytes (HEKs) and the cutaneous squamous cell carcinoma cell line COLO-16. Apigenin treatment reduced microtubule-associated protein 1 light chain 3 (LC3)-II turnover, acridine orange staining and GFP-LC3 puncta in both cell types, suggesting autophagy inhibition. However, apigenin treatment restored the inhibition of autophagy in UVB-challenged HEKs. Moreover, apigenin treatment restored the UVB-induced downregulation of ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia, Rad3-related (ATR) and the unfolded protein response (UPR) regulatory proteins, BiP, IRE1α and PERK in HEKs. Apigenin treatment also inhibited UVB-induced apoptosis and cell death in HEKs. In addition, autophagy inhibition by autophagy-related gene (ATG) 5 RNA interference interrupted apigenin-induced restoration of ATR, ATM and BiP, which were downregulated in HEKs exposed to UVB radiation. Our findings indicate that apigenin exhibits a novel protective effect in keratinocytes with UVB damage, suggesting potential application as a photoprotective agent.
紫外线（UV）-B 辐射是导致许多皮肤癌发生和发展的主要环境风险因素。芹菜素是一种生物类黄酮，据报道可抑制 UVB 诱导的皮肤癌。然而，芹菜素在 UV 损伤的角质细胞中的作用机制尚不清楚。在这项研究中，通过乳酸脱氢酶（LDH）释放试验，我们发现芹菜素处理增加了原代人表皮角质细胞（HEKs）和皮肤鳞状细胞癌细胞系 COLO-16 的细胞死亡。芹菜素处理减少了微管相关蛋白 1 轻链 3（LC3）-II 的转化、吖啶橙染色和两种细胞类型中的 GFP-LC3 斑点，表明自噬抑制。然而，芹菜素处理恢复了 UVB 挑战的 HEKs 中自噬的抑制。此外，芹菜素处理恢复了 UVB 诱导的共济失调毛细血管扩张突变（ATM）、共济失调毛细血管扩张症、Rad3 相关（ATR）和未折叠蛋白反应（UPR）调节蛋白 BiP、IRE1α 和 PERK 在 HEKs 中的下调。芹菜素处理还抑制了 HEKs 中的 UVB 诱导的细胞凋亡和细胞死亡。此外，自噬相关基因（ATG）5 RNA 干扰抑制自噬会中断芹菜素诱导的 ATR、ATM 和 BiP 的恢复，这些蛋白在暴露于 UVB 辐射的 HEKs 中下调。我们的研究结果表明，芹菜素在 UVB 损伤的角质细胞中表现出一种新的保护作用，提示其可能作为一种光保护剂应用。
