Identification of a natural compound, sesamin, as a novel TRPM8 antagonist with inhibitory effects on prostate adenocarcinoma.

Identification of a natural compound, sesamin, as a novel TRPM8 antagonist with inhibitory effects on prostate adenocarcinoma. Fitoterapia. 2020 May 18;:104631 Authors: Sui Y, Li S, Zhao Y, Liu Q, Qiao Y, Feng L, Li S Abstract Transient receptor potential melastatin 8 (TRPM8) is a calcium ion-permeable cation channel that is used as a prognostic marker and therapeutic target for different tumor types. To identify natural selective TRPM8 antagonists, we tested 158 traditional Chinese medicine (TCM) compounds for the ability to inhibit TRPM8. Calcium mobilization assays were used to evaluate the 158 TCM compound components in HEK293 cells stably expressing TRPM8. An identified putative TRPM8 antagonist, sesamin, was further evaluated. Publicly available cancer OMICS data were used to explore the expression of TRPM8, its gene regulatory network, and the survival of patients with prostate adenocarcinoma (PRAD). The cytotoxicity and specificity of sesamin to TRPM8 were tested in HEK293/TRPM8 cells. The effect of sesamin on cell proliferation in PRAD cell lines was assessed. Sesamin selectively inhibited TRPM8 in HEK293/TRPM8 cells (IC50: 9.78 μM), and a molecular docking study confirmed the binding of sesamin to TRPM8. TRPM8 was highly overexpressed in PRAD, and high TRPM8 expression was associated with poor survival of PRAD patients. Functional network analysis suggested that TRPM8 has key effects on proliferation, survival, and invas...
Source: Fitoterapia - Category: Biochemistry Authors: Tags: Fitoterapia Source Type: research