Work

KDM1A inhibition increases UVA toxicity and enhances photodynamic therapy efficacy

Year: 2022

Type: article

Abstract: Background Lysine‐specific histone demethylase 1 (KDM1A/LSD1) regulates multiple cellular functions, including cellular proliferation, differentiation, and DNA repair. KDM1A is overexpressed in squamous cell carcinoma of the skin and inhibition of KDM1A can suppress cutaneous carcinogenesis. Despite the role of KDM1A in skin and DNA repair, the effect of KDM1A inhibition on cellular ultraviolet (UV) response has not been studied. Methods The ability of KDM1A inhibitor bizine to modify cell death after UVA and UVB exposure was tested in normal human keratinocytes and melanocytes, HaCaT, and FaDu cell lines. KDM1A was also downregulated using shRNA and inhibited by phenelzine in HaCaT and FaDu cells to confirm the role of KDM1A in UVA response. In addition, cellular reactive oxygen species (ROS) changes were assessed by a lipid‐soluble fluorescent indicator of lipid oxidation, and ROS‐related gene regulation using qPCR. During photodynamic therapy (PDT) studies HaCaT and FaDu cells were treated with aminolaevulinic acid (5‐ALA) or HPPH (2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide‐a) sodium and irradiated with 0‐8 J/cm2 red LED light. Results KDM1A inhibition sensitized cells to UVA radiation‐induced cell death but not to UVB. KDM1A inhibition increased ROS generation as detected by increased lipid peroxidation and the upregulation of ROS‐responsive genes. The effectiveness of both ALA and HPPH PDT significantly improved in vitro in HaCaT and FaDu cells after KDM1A inhibition. Conclusion KDM1A is a regulator of cellular UV response and KDM1A inhibition can improve PDT efficacy.

Source: Photodermatology Photoimmunology & Photomedicine

DOI: 10.1111/phpp.12826