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Investigational New Drugs 04/2012; · 3.36 Impact Factor
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ABSTRACT: We investigated the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers of the neem tree (Azadirachta indica) on human choriocarcinoma (BeWo) cells. Treatment with nimbolide resulted in dose- and time-dependent inhibition of growth
of BeWo cells with IC50 values of 2.01 and 1.19μM for 7 and 24h respectively, accompanied by downregulation of proliferating cell nuclear antigen.
Examination of nuclear morphology revealed fragmentation and condensation indicating apoptosis. Increase in the generation
of reactive oxygen species (ROS) that was reversed by addition of reduced glutathione suggested ROS involvement in the cytotoxicity
of nimbolide. A decrease in Bcl-2/Bax ratio with increased expression of Apaf-1 and caspase-3, and cleavage of poly(ADP-ribose)
polymerase provide compelling evidence that nimbolide-induced apoptosis is mediated by the mitochondrial pathway. The results
of the present study suggest that nimbolide has immense potential in cancer prevention and therapy based on its antiproliferative
and apoptosis inducing effects.
KeywordsApoptosis-Bcl-2/Bax-Neem-Nimbolide-PCNA-Reactive oxygen species
Investigational New Drugs 04/2012; 27(3):246-252. · 3.36 Impact Factor
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ABSTRACT: Limonoids from the neem tree (Azadirachta indica) have attracted considerable research attention for their cytotoxicity against human cancer cell lines. However, the antiproliferative and apoptosis inducing effects of neem limonoids have not been tested in animal tumour models. The present study was therefore designed to evaluate the relative chemopreventive potential of the neem limonoids azadirachtin and nimbolide in the hamster buccal pouch (HBP) carcinogenesis model by analyzing the expression of proliferating cell nuclear antigen (PCNA), p21(waf1), cyclin D1, glutathione S-transferase pi (GST-P), NF-kappaB, inhibitor of kappaB (IkappaB), p53, Fas, Bcl-2, Bax, Bid, Apaf-1, cytochrome C, survivin, caspases-3, -6, -8 and -9, and poly(ADP-ribose) polymerase (PARP) by RT-PCR, immunohistochemical, and Western blot analyses. The results provide compelling evidence that azadirachtin and nimbolide mediate their antiproliferative effects by downregulating proteins involved in cell cycle progression and transduce apoptosis by both the intrinsic and extrinsic pathways. On a comparative basis, nimbolide was found to be a more potent antiproliferative and apoptosis inducing agent and offers promise as a candidate agent in multitargeted prevention and treatment of cancer.
Investigational New Drugs 06/2009; 28(4):392-401. · 3.36 Impact Factor
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ABSTRACT: We investigated the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers of the neem tree (Azadirachta indica) on human choriocarcinoma (BeWo) cells. Treatment with nimbolide resulted in dose- and time-dependent inhibition of growth of BeWo cells with IC(50) values of 2.01 and 1.19 microM for 7 and 24 h respectively, accompanied by downregulation of proliferating cell nuclear antigen. Examination of nuclear morphology revealed fragmentation and condensation indicating apoptosis. Increase in the generation of reactive oxygen species (ROS) that was reversed by addition of reduced glutathione suggested ROS involvement in the cytotoxicity of nimbolide. A decrease in Bcl-2/Bax ratio with increased expression of Apaf-1 and caspase-3, and cleavage of poly(ADP-ribose) polymerase provide compelling evidence that nimbolide-induced apoptosis is mediated by the mitochondrial pathway. The results of the present study suggest that nimbolide has immense potential in cancer prevention and therapy based on its antiproliferative and apoptosis inducing effects.
Investigational New Drugs 09/2008; 27(3):246-52. · 3.36 Impact Factor
