Epigarcinol and isogarcinol isolated from the root of Garcinia ovalifolia induce apoptosis of human promyelocytic leukemia (HL-60 cells)

BACKGROUND: Plants from garcinia genus have been used for centuries against several diseases. OBJECTIVE: This study aimed to investigate the mechanism of apoptosis induced by epigarcinol and isogarcinol isolated from the root of Garcinia ovalifolia (Clusiaceae) on human promyelocytic leukemia (HL-60 cells). METHODS: Epigarcinol and isogarcinol were isolated from the root of G. ovalifolia by using column chromatography method. The antiproliferative property of these molecules and fractions were assessed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The light fluorescence microscope was utilized to observe the morphological changes of HL-60 cells after 24 h treatment. Early apoptosis and cell cycle distribution were analyzed by using flow cytometry (FCM). RESULTS: The results showed that epigarcinol and isogarcinol inhibited the proliferation of HL-60 and PC-3 cells in a concentration-dependent manner with IC(50) varying between 4 and 76 µg/mL depending on the cell line and the molecule. The apoptosis rate and the number of apoptotic cells significantly increased with the augmentation of the concentration of the molecules. The results of flow cytometry (FCM) indicated that epigarcinol and isogarcinol induced significant G(2)/S arrest of HL-60 cells, the disruption of mitochondrial membrane potential and reactive oxygen species (ROS) generation. CONCLUSION: These results indicated that epigarcinol and isogarcinol demonstrated in vitro antiproliferative properties and induce apoptosis of HL-60 cells which is related to the G(2)/S arrest, and it exerts its apoptotic effect through the loosing of mitochondrial membrane potential.