Effects of 4F-phenyl pyrazole, a [6]-shogaol derivative, on colorectal adenocarcinoma cell death

Abstract

Colorectal cancer remains a leading cause of cancer-related mortality globally. Apoptosis induction is a crucial target for developing effective chemotherapeutics. [6]-shogaol, a ginger-derived compound, has demonstrated anticancer potential by triggering apoptosis in various cancer types. This study investigated the apoptosis- and autophagy-inducing and antiproliferative effects of 4F-phenyl pyrazole, a synthetic [6]-shogaol derivative, in colorectal adenocarcinoma cells. Our findings demonstrated that 4F-phenyl pyrazole effectively reduced colorectal adenocarcinoma HT29 cell viability, showing comparable efficacy to [6]-shogaol with an IC50 of 9.7 µM. It also significantly inhibited colony formation, indicating its antiproliferative properties. Mechanistic studies revealed dose-dependent increases in phosphatidylserine exposure and anoctamin6 (ANO6) expression at 10, 20, and 40 µM after 72 h of 4F-phenyl pyrazole treatment, suggesting apoptosis induction. Similar dose-dependent effects were observed for LC3 expression, a marker of autophagy. Furthermore, 40 µM 4F-phenyl pyrazole treatment resulted in diminished spheroid formation. These results suggest that 4F-phenyl pyrazole is a promising candidate for further development as an anticancer agent. Further investigations into its therapeutic potential and underlying mechanisms are warranted.