Madhuca longifolia bark extract as an adjunct to the treatment of colon carcinoma cells with SN-38: a synergistic combination with potent activity

Background – Plants have been used by humans as a source of food, spices, and medicines since prehistoric times. Madhuca longifolia is a tree native to South Asia. In traditional medicine of the region, extracts from different parts of this plant are used to treat inflammation, ulcers, epilepsy, diabetes, and rheumatism. Methods – Cytotoxicity of the extract from the bark of M. longifolia and its fractions was assessed via sulforhodamine B (SRB) assay in human colorectal cancer cell lines HT-29 and HCT116, as well as normal epithelial cells FHC. The effects on cell cycle progression, apoptosis induction, and reactive oxygen species (ROS) production were studied by flow cytometry. The existence of synergy between the extract and active form of irinotecan, SN-38, was investigated by means of CompuSyn software. Results – Aqueous ethanolic extract from M. longifolia was demonstrated to exhibit potent cytotoxic effect in human colon cancer cells. The studied extract and its fractions exhibited some degree of selectivity, since they were more toxic to cancer cells than to normal colon epithelium. Additionally, the extract and its fractions turned out to potentiate anticancer effect of SN-38 used in concentrations that were non-toxic to the cells. The most active extract was shown to induce apoptosis and increase ROS production in cancer cells. The anticancer effect of the combination of SN-38 and M. longifolia extract increased even further when the extract was applied to the cells a few hours before the drug. These results indicate that M. longifolia bark extract sensitized colon cancer cells to SN-38. Conclusion – These findings provide pharmacological support for the traditional use of M. longifolia and suggest that its bark extract may constitute a source of promising adjunct substances that could be potentially used in therapy in order to decrease the concentrations of irinotecan applied to the patients and, in this way, reduce side-effects of the drug.