The natural extract degalactotigonin exerts antitumor effects on renal cell carcinoma cells through repressing YAP.

Abstract

BackgroundThe pervasive progression of renal cell carcinoma (RCC) after treatment demands more effective drugs with few side effects. In the present study, we determined whether degalactotigonin (DGT) extracted from Solanum nigrum L. could exert antitumoral effects on RCC and examined the related molecular mechanisms.MethodsThe effects of DGT on RCC cells were assessed by cell counting kit-8 (CCK-8) assay, flow cytometry, invasion and migration assays and subcutaneous tumor xenograft experiments in nude mice. The related molecular mechanisms were delineated by RNA sequencing (RNA-seq), real-time polymerase chain reaction (PCR), western blotting, coimmunoprecipitation (co-IP) and plasmid transfection.ResultsDGT induced apoptosis and suppressed the proliferation, invasion, migration, and tumorigenicity of RCC cells. Mechanistically, yes-associated protein (YAP) signaling was inactivated, and the expression of YAP and its target genes was reduced in degalactotigonin-treated RCC cells. Additionally, DGT activated phosphorylated large tumor suppressor 1/2 (p-LATS1/2) to phosphorylate YAP, which increased YAP retention in the cytoplasm but decreased the amount of YAP that entered the nuclei of RCC cells. Moreover, DGT impaired the increased aggressive features of RCC cells induced by YAP overexpression.ConclusionsDGT is an effective therapeutic agent, which facilitates the apoptosis and inhibits the proliferation, invasion, migration, and tumorigenicity of RCC cells in a YAP-dependent manner.