Cytotoxic compounds from the leaves of Combretum paniculatum Vent
Combretum paniculatum Vent. (Combretaceae) is a shrub that is widespread in tropical Africa. It is used locally in the treatment of carcinomous tumors. The cytotoxic activity of pheophorbide a and pheophorbide a-methyl ester isolated from the leaves of C. paniculatum were investigated. In vitro cytotoxicity of the compounds were evaluated against HT-29, MCF-7 and HeLa cancer cell lines using the methyl thiazolyl tetrazolium (MTT) assay and peripheral blood mononuclear cells. Cell cycle analysis was performed using propidium iodide staining and flow cytometry. Pheophorbide a was more toxic to MCF-7 and HeLa cells than its methyl ester, while the opposite result was seen in HT-29 cells. The methyl ester killed all the peripheral blood mononuclear cells from healthy donor blood while less inhibition was observed with pheophorbide a. Both compounds induced cell cycle arrest in HeLa cells in the G0/G1 phase, with pheophorbide a-methyl ester yielding a more enhanced G1/G0 arrest. After 24 h of exposure, the percentage of HeLa cells in the G0/G1 phase was 38.5% in vehicle control cells, 55.9% in pheophorbide a and 70.0% in pheophorbide a-methyl ester treated cells. The in vitro effect of C. paniculatum on cancer cell lines may be ascribed to the presence of pheophorbide a and its methyl ester. They exert this effect through the induction of cell cycle arrest in the G0/G1 phase of the cell cycle.
Key words: Cytotoxicity, cancer, Combretum, pheophorbide a, pheophorbide a-methyl ester.