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01-08-2010 | PRECLINICAL STUDIES

The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis

Authors: G. Harish Kumar, R. Vidya Priyadarsini, G. Vinothini, P. Vidjaya Letchoumy, S. Nagini

Published in: Investigational New Drugs | Issue 4/2010

Summary

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-κB, inhibitor of κB (IκB), 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.

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Title: The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis
Authors: G. Harish Kumar
R. Vidya Priyadarsini
G. Vinothini
P. Vidjaya Letchoumy
S. Nagini
Publication date: 01-08-2010
Publisher: Springer US
Published in: Investigational New Drugs / Issue 4/2010
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-009-9263-3

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