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

摘要

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