Dual Modulation of Autophagy and Apoptosis as Anticancer Mechanism of Action of Khaya grandiofoliola in Colon Carcinoma Cells

<i>Khaya grandiofoliola</i> (Kh) is a medicinal plant with therapeutic properties. Studies have reported on the general bioactivity and anticancer potentials of the plant, but no investigations have yet investigated its anticancer mechanism of action. This study presents the first examination of the anticancer mechanism of action of the methanolic extract of Kh, alongside phytochemical profiling of its anticancer constituents. We conducted in vitro investigations into the mechanism of action of Kh and performed bioactivity-guided fractionation, with subsequent identification of its anticancer phytochemicals using HPLC and GC-MS, respectively. Kh posed a potent antiproliferative effect against colon carcinoma cells and an antioxidant property at low microgram levels. Furthermore, the treatment of Kh in <i>Caco-2</i> cells led to the accumulation of p62 puncta, indicating inhibition of autophagic flux degradation. Kh impacts microtubule, induced G1 arrest, and late apoptosis induction in <i>Caco-2</i> cells. Phytochemicals belonging to sesquiterpene alcohols were found most abundant in the Kh bioactive fractions. The identified phytochemicals are potential inducers of apoptosis, autophagy flux inhibition, and G1-phase arrest. Our findings suggest that the anticancer property of Kh is mediated through the dual modulation of autophagy and apoptosis. Further studies are needed to isolate the active compounds responsible for these effects and further elucidate the underlying molecular mechanisms.