Mangifera zeylanica and Mangifera indica Leaf Extracts Exert Anticancer Effects Possibly by Inhibiting Histone Deacetylases

ABSTRACT Mangifera indica L. is a popular and widely available plant. Mangifera zeylanica Hook.f. is a plant endemic to Sri Lanka. Both plants bare edible fruits and possess medicinal properties. In the present study, potential anticancer effects of M. zeylanica and M. indica leaves were investigated in lung cancer cells. Hexane, chloroform, ethyl acetate, and methanol extracts of leaves from both plants were obtained using sequential extraction. Chloroform extract of M. zeylanica leaves (MZC) and ethyl acetate extract of M. indica leaves (MIEA) inhibited the proliferation, migration, and colony formation. These extracts showed low cytotoxicity in MRC-5 normal lung fibroblast cells. Furthermore, DNA fragmentation analysis and ethidium bromide/acridine orange (AO/EB) staining showed that MZC and MIEA can induce apoptosis. Gene expression analysis by real-time PCR identified that MZC and MIEA can regulate the expression of apoptosis-associated genes p53, Bax, and survivin. In addition, treatment of both MZC and MIEA decreased histone deacetylase (HDAC) activity, indicating the HDAC inhibitory potentials of leaf extracts. Liquid chromatography-mass spectrometry (LC-MS) identified the presence of mangiferin, 6-geranylnaringenin, nodakenin, and pyrogallol in both leaf extracts as major phytochemicals. Overall, our findings indicate that M. zeylanica and M. indica leaf extracts exert anticancer activity by decreasing the proliferation of non-small lung cancer cells possibly through the inhibition of the activity of HDACs, a major class of enzymes implicated in epigenetic modifications. This investigation provides a rationale to isolate compounds with anticancer and HDAC inhibitory potentials from M. zeylanica and M. indica leaves.