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Antiproliferative effect on human cancer cell lines after treatment with nimbolide extracted from an edible part of the neem tree ( Azadirachta indica )
Author(s) -
Roy Molay Kumar,
Kobori Masuko,
Takenaka Makiko,
Nakahara Kazuhiko,
Shinmoto Hiroshi,
Isobe Seiichiro,
Tsushida Tojiro
Publication year - 2007
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.2058
Subject(s) - azadirachta , apoptosis , u937 cell , cell culture , biology , cell cycle , traditional medicine , cancer cell , cell growth , pharmacology , botany , medicine , cancer , biochemistry , genetics
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.