Antiproliferative effect on human cancer cell lines after treatment with nimbolide extracted from an edible part of the neem tree (Azadirachta indica)

Nimbolide, a triterpenoid extracted from the flowers of the neem tree (Azadirachta indica), was found to have antiproliferative activity against some cancer cell lines. Treatment of cells with 0.5-5.0 microm concentrations of nimbolide resulted in moderate to very strong growth inhibition in U937, HL-60, THP1 and B16 cell lines. Flow cytometric analysis of U937 cells showed that nimbolide treatment (1-2.5 microm) resulted in cell cycle disruption by decreasing the number of cells in G0/G1 phase, with initial increases in S and G2/M phases. Cells exposed to a higher dose of nimbolide for a longer period displayed a severely damaged DNA profile, resulting in a remarkable increase in the number of cells in the sub-G1 fraction, with a reciprocal decrease of cells in all phases. Quantification of the expression of phosphatidylserine in the outer cell membrane showed that doses of nimbolide higher than 0.4 microm exerted remarkable lethality, with over 60% of cells exhibiting apoptotic features after exposure to 1.2 microm nimbolide. The antiproliferative effect of nimbolide and its apoptosis-inducing property raise hope for its use in anticancer therapy by enhancing the effectiveness of cell cycle disruption.