Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells.
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.
Harish Kumar
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G
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.
Chandra Mohan
K V P
KV
Jagannadha Rao
A
A
Nagini
S
S
D017209:Apoptosis / Q000187:drug effects*; D031601:Azadirachta / Q000737:chemistry*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000188:drug therapy / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D036701:Limonins / Q000494:pharmacology* / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000378:metabolism; D008517:Phytotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism
D036701:Limonins; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; C042198:nimbolide