Anti-angiogenic and cytotoxic activities of rotenoids from Derris trifoliata Lour.

Abstract

This study aimed to isolate metabolites of D. trifoliata stem and to evaluate their cytotoxic and anti-angiogenic activities. Chromatographic fractionation of the EtOAc led to the isolation of eight known rotenoids (1-2, 4-6, 11-12 and 15). All compounds were first evaluated for their cytotoxicity against three cancer cell lines; human cervical carcinoma (CaSki), colon cancer (HCT-116), hepato carcinoma (Hep-G2) and normal human colon epithelial (CCD841) cells. All Compounds showed cytotoxicity against HCT-116 with IC50 ranging 0.12-11.21 µM, while they were weak or no activity against Hep-G2 and CaSKi cells. Moreover, it was found that 12a-hydroxyrotenone (11) potently inhibited migration of colon cancer HCT-116 cells (>90% inhibition at 0.5 µM). Further, all isolated compounds were evaluated for anti-angiogenic activity. Results indicated that 12a-hydorxyrotenone (11) displayed promising anti-angiogenic activity in both ex vivo and in vitro assays, as well as it mainly functions by suppression of endothelial cells (ECs) proliferation and tube formation, but did not show any significant effect on ECs migration. This is the first study providing the evidence that compound 11 has high potency on HCT-116 cancer growth and migration, as well as it is a potent anti-angiogenic agent. Thus, compound 11 may be suitable for use as a lead compound or for further development to overcome cancer metastasis.