Sutherlandia frutescens treatment induces apoptosis and modulates the PI3-kinase pathway in colon cancer cells

Abstract

Sutherlandia frutescens is a plant that is endemic to South Africa and is traditionally used for the treatment of cancer and many other ailments. Although previous studies have shown S. frutescens to exert anti-proliferative and apoptotic effects in human mammary adenocarcinoma- and leukemia cell lines, its potential cytotoxic effects on colon cancer cells have not yet been established. Moreover, limited information is available elucidating the major signaling pathways involved upon exposure to the herbal extract. The aim of this study was therefore to assess the cytotoxic effect of S. frutescens on the colon cancer cell line CaCo2, to investigate molecular role players of apoptosis and to assess the involvement of the PI3-K survival pathway. CaCo2 cells exposed to ethanolic extracts of S. frutescens showed significant decreased cell viability, indicated by reduced MTT reductive capacity, increased pyknosis as well as loss in cellular membrane integrity. Western blot analysis revealed a down-regulation in the PI3-K and Akt phosphorylation, a decrease in forkhead transcription factor (FKHR) phosphorylation as well as a concomitant induction of apoptosis. This study demonstrates that Sutherlandia treatment attenuates proliferation of colon cancer cells in vitro by the disruption of the key molecules in the PI-3K pathway thereby inducing apoptosis.