Kaempferol Inhibits Cervical Cancer Cells by Inducing Apoptosis and Autophagy via Inactivation of the PI3K/AKT/mTOR Signaling Pathway

Background/Aim: Kaempferol, a natural flavonoid, occurs abundantly in fruits and vegetables. It has various bioactivities, with antioxidant, anti-inflammatory, and other beneficial properties. The aim of this study was to investigate the in vitro effects of kaempferol on the proliferation, apoptosis, and autophagy of KB cells, a human cervical cancer cell line, and the corresponding action mechanisms. Materials and Methods: The inhibitory efficacy of kaempferol on KB cervical cancer cells was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide assay, migration assay, 4',6diamidino-2-phenylindole staining, flow cytometry, acridine orange staining and western blotting. Results: Kaempferol reduced KB cell viability and migration in a dose-dependent manner. Additionally, kaempferol-induced apoptosis was confirmed, and kaempferol treatment influenced levels of apoptotic proteins. Autophagy was detected upon visualization of characteristic autophagic vacuoles and acidic vesicular organelles, and verified using western blotting, which revealed elevated levels of autophagy-related proteins. Kaempferolmediated apoptosis and autophagy were evidently attributable to reduced phosphorylation in the phosphoinositide 3-kinase (PI3K)/serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR) pathway. This finding was validated using a pharmacological inhibition assay with the PI3K pathway inhibitor LY294002, which promoted KB cell apoptosis and autophagy. Conclusion: Our results suggest that kaempferol induces apoptosis and autophagy by inhibiting the PI3K/AKT/mTOR pathway in human cervical cancer cells, empirically showing the anticancer effects of kaempferol, and thereby presenting it as a potential anticancer therapeutic agent.