Handelin protects human skin keratinocytes against ultraviolet B-induced photodamage via autophagy activation by regulating the AMPK-mTOR signaling pathway

• Published in: Archives of biochemistry and biophysics Vol. 743; p. 109646
• Main Authors: Chu, Jimin, Xiang, Yang, Lin, Xianghong, He, Miao, Wang, Yan, Ma, Qiong, Duan, Jingxian, Sun, Sujiao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2023
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Autophagy; Cell Line; Handelin; Humans; Keratinocytes; mTOR; Photodamage; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; Ultraviolet Rays - adverse effects; UVB; UVB; mTOR; AMPK; Photodamage; Handelin; Autophagy
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2023.109646

Handelin is a natural ingredient extracted from Chrysanthemum boreale flowers that has been shown to decrease stress-related cell death, prolong lifespan, and promote anti-photoaging. However, whether handelin inhibits ultraviolet (UV) B stress-induced photodamage remains unclear. In the present study, we investigate whether handelin has protective properties on skin keratinocytes under UVB irradiation. Human immortalized keratinocytes (HaCaT keratinocytes) were pretreated with handelin for 12 h before UVB irradiation. The results indicated that handelin protects keratinocytes against UVB-induced photodamage by activating autophagy. However, the photoprotective effect of handelin was suppressed by an autophagic inhibitor (wortmannin) or the transfection of keratinocytes with a small interfering RNA targeting ATG5. Notably, handelin reduced mammalian target of rapamycin (mTOR) activity in UVB-irradiated cells in a manner similar to that shown by the mTOR inhibitor rapamycin. Adenosine monophosphate-activated protein kinase (AMPK) activity was also induced by handelin in UVB-damaged keratinocytes. Finally, certain effects of handelin, including autophagy induction, mTOR activity inhibition, AMPK activation, and reduction of cytotoxicity, were suppressed by an AMPK inhibitor (compound C). Our data suggest that handelin effectively prevents photodamage by protecting skin keratinocytes against UVB-induced cytotoxicity via the regulation of AMPK/mTOR-mediated autophagy. These findings provide novel insights that can aid the development of therapeutic agents against UVB-induced keratinocyte photodamage. [Display omitted] •Handelin can prevent UVB-irradiated skin photodamage.•Handelin can induce autophagy and reverse UVB-induced autophagy decreases in keratinocytes.•Handelin can activate autophagy by regulating AMPK-mTOR signaling.