The Effects of Combining Cancer Drugs with Compounds Isolated from Combretum zeyheri Sond. and Combretum platypetalum Welw. ex M.A. Lawson (Combretaceae) on the Viability of Jurkat T Cells and HL-60 Cells.

Abstract

Combretum zeyheri and Combretum platypetalum have been shown to have anticancer, antibacterial, antituberculosis, and antifungal effects in both in vivo and in vitro studies. This study sought to evaluate the antiproliferative effects of compounds isolated from C. zeyheri and C. platypetalum on Jurkat T and HL-60 cancer cell lines in combination with doxorubicin and/or chlorambucil. At their GI50 concentrations, the isolated compounds were combined with the corresponding GI50 of chlorambucil and doxorubicin. The cytotoxic effects of the combined compounds were determined on BALB/c mouse peritoneal cells. All the 4 isolated compounds had significant cytotoxic effects on Jurkat T cells. Compounds CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) had GI50s on Jurkat T cells of 3.98, 19.33, 6.82, and 20.28 μg/ml, respectively. CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) showed GI50s of 14.18, 28.69, 29.87, and 16.46 μg/ml on HL-60 cancer cell lines, respectively. The most potent combination against Jurkat T cells was found to be CP 404 (1) and chlorambucil. This combination showed no cytotoxic effects when tested on BALB/c mouse peritoneal cells. It was concluded that the compounds extracted from C. zeyheri and C. platypetalum inhibit the growth of Jurkat T cells in vitro. The combination of the compounds with anticancer drugs enhanced their anticancer effects. The combination of CP 404 (1) and chlorambucil was found not to be toxic to normal mammalian cells. Therefore, CP 404 (1), 3-O-β-L-rrhamnopyranosyl-5,7,3′4′,5′-pentahydroxyflavone, has the potential to be a source of lead compounds that can be developed for anticancer therapy. Further structure-activity relationship studies on this compound are warranted.