Antitumor and apoptotic effects of 5-methoxypsoralen in U87MG human glioma cells and its effect on cell cycle, autophagy and PI3K/Akt signaling pathway

INTRODUCTION: The main purpose of the current study was to investigate the antitumor effects of 5-methoxypsoralen in U87MG human glioma cells along with studying its effects on cell cycle progression, autophagy and the PI3K/Akt signaling pathway. MATERIAL AND METHODS: The cytotoxic effects of the drug were demonstrated by the MTS cell viability assay while its effects on cellular morphology associated with cell apoptosis were evaluated by phase contrast and fluorescence microscopic techniques. Effects of 5-methoxypsoralen on the cell cycle were studied by flow cytometry while effects on PI3K/Akt proteins were evaluated by western blot assay. RESULTS: The results indicate that 5-methoxypsoralen led to time-dependent as well as dose-dependent inhibitory effects on U-87MG human glioma cells. 5-Methoxypsoralen led to a substantial decrease of cell count along with distorted cell morphology. The molecule also led to DNA ladder formation which increased with increasing doses of 5-methoxypsoralen. 5-methoxypsoralen also led to dose-dependent G2/M phase cell cycle arrest. 5-Methoxypsoralen-treated cells also exhibited altered cell ultrastructure with the appearance of autophagic vacuoles and the number of these vacuoles increased with increasing drug dose. CONCLUSIONS: In brief, the results indicate that 5-methoxypsoralen exerted potent anticancer and apoptotic effects in U-87MG human glioma cells along with inducing cell cycle arrest, autophagy and m-TOR/PI3K/Akt signaling pathway inhibition.