Anticancer Effect of a New Benzophenanthridine Isolated from Zanthoxylum madagascariense (Rutaceline)

Fractionation of the cyclohexane extract from the stem bark powder of Zanthoxylum madagascariense led to the isolation of a new benzophenanthridine-type alkaloid, hydrochloride of 2,3-methylendioxy-8-hydroxy-7-methoxy-benzo[C]phenanthridine (Rutaceline), characterized on the basis of its spectral data. Rutaceline was evaluated for its antiproliferative capacity on the human colorectal adenocarcinoma (Caco-2) and the African green monkey kidney (Vero) cell lines. The 50% inhibition of cell growth (IC 50 ) obtained after 24 h incubation was similar for both cells lines (110-115 μg/ml, i.e. 269-281 μM), but at 48 h the IC 50 value for the Caco-2 cells was lower than for the Vero cells (20 μg/ml, i.e. 49 μM versus 90 μg/ml, i.e. 220 μM) indicating a higher cell growth inhibitory effect on the colon adenocarcinoma cells. At the respective IC 50 concentrations, Rutaceline did not significantly induce apoptosis but induced cell cycle arrest in the G0/G1 phase, as well as a decrease of cells in S phase. Rutaceline also induced DNA fragmentation in both cell lines, as revealed by agarose gel electrophoresis, and a dose-dependent clastogenic effect in both cell lines as revealed by the Comet assay.