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.
Keywords: Apigenin; Autophagy; Keratinocyte; Ultraviolet B.
Copyright © 2019. Published by Elsevier B.V.