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Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells

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An Erratum to this article was published on 27 April 2012

Summary

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 1.19 μM 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.

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Acknowledgements

This work was supported by a grant from the Department of Science and Technology, New Delhi, India. AJ Rao is a recipient of the Ramanna Fellowship from the Department of Science and Technology, Govt. of India.

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Correspondence to S. Nagini.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10637-012-9816-8

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Harish Kumar, G., Chandra Mohan, K., Jagannadha Rao, A. et al. Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells. Invest New Drugs 27, 246–252 (2009). https://doi.org/10.1007/s10637-008-9170-z

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