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 μ m 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 μ m ) 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 μ m exerted remarkable lethality, with over 60% of cells exhibiting apoptotic features after exposure to 1.2 μ m 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. Copyright © 2006 John Wiley & Sons, Ltd.