LAUSR

Skin photoaging, skin inflammation and skin cancer are related with excessive exposure to solar ultraviolet light (solar-UV). PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a member of the serine/threonine protein kinase, which regulates the signaling cascades of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal regulated kinase 1/2 (ERK1/2). PBK/TOPK plays a significant role in solar-UV-induced cutaneous basal cell carcinoma (cutaneous-BCC), and targeting PBK/TOPK can be supposed to treat and prevent cutaneous-BCC. Herein, The clinical samples showed that the expression levels of PBK/TOPK, phosphor-p38 MAPK and phosphor-ERK1/2 were up-regulated in cutaneous-BCC tissues of human. In HaCaT cells, the expression of phosphor-p38 MAPK or phosphor-ERK1/2 increased in a dose and time dependent manner after solar-UV treatment. MTT cytotoxicity assay results showed that HaCaT cells acitivity have no effect after 0-200 µM Gossypetin treatment in 0-72 h. In vitro kinase assay and Microscale thermophoresis (MST) assay results showed that Gossypetin bound with PBK/TOPK and suppressed PBK/TOPK activity, the lowest equilibrium dissociation constant (Kd) of them is 15.5±1.6 µM. Ex vivo results showed Gossypetin inhibited solar-UV-induced phosphorylation of PBK/TOPK, p38 MAPK, ERK1/2 and H2AX by suppressing PBK/TOPK activity. In vivo test results indicated that Gossypetin suppressed solar-UV-induced increase of PBK/TOPK, phosphor-p38 MAPK, phosphor-ERK1/2 and phosphor-H2AX in SKH-1 hairless mice. In summary, our data demonstrated that Gossypetin can alleviate solar-UV-induced cutaneous-BCC by blocking PBK/TOPK, and Gossypetin could be a remarkable agent for treating solar-UV induced cutaneous basal cell carcinoma.