(2E)-1-(2,4,6-trimethoxyphenyl)-3-(3-nitrophenyl)-2-propen-1-one Promotes Apoptosis By Regulating ERK/MAPK Pathway In Hepatocellular Carcinoma Cells

Abstract (2E)-1-(2,4,6-trimethoxyphenyl)-3-(3-nitrophenyl)-2-propen-1-one (TMONC), a chalcone derivative, exhibits pro-apoptotic potential in tumor cells. However, its antitumor activity has not yet been elucidated. In this study, we report that TMONC significantly inhibited proliferation, and accelerated apoptosis of hepatocellular carcinoma (HCC) cells. Interrupted apoptotic signals indicated that TMONC activated the mitochondria-dependent apoptotic pathway. In addition, TMONC induced the G2/M arrest. RNA sequencing analysis suggested the ERK/MAPK signaling was the most significantly enriched pathway. Furthermore, reverse docking analysis revealed that ERK1 and PARP-1 had the two highest score across all docked targets. TMONC significantly inhibited the expression of RAS, ERK, p-ERK, c-Myc and c-Fos in HCC cells. Therefore, TMONC is a multi-target compound, which shows anti-cancer activity by suppressing the ERK/MAPK pathway. This may provide a potential therapeutic strategy by inducing apoptosis to treat HCC.