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

• Published in: Investigational new drugs Vol. 27; no. 3; pp. 246 - 252
• Main Authors: Harish Kumar, G., Chandra Mohan, K.V.P., Jagannadha Rao, A., Nagini, S.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2009; Springer Nature B.V
• Subjects: Antibiotics; Antigens; Antioxidants; Apoptosis; Apoptosis - drug effects; Azadirachta - chemistry; Azadirachta indica; Biochemistry; Cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Choriocarcinoma - drug therapy; Choriocarcinoma - pathology; Clinical outcomes; Cytotoxicity; Drug dosages; Drug Screening Assays, Antitumor; Experiments; Humans; Intracellular Space - drug effects; Intracellular Space - metabolism; Limonins - pharmacology; Limonins - therapeutic use; Medicine; Medicine & Public Health; Morphology; Neoplasm Proteins - metabolism; Oncology; Pharmacology; Pharmacology/Toxicology; Phytochemicals; Phytotherapy; Preclinical Studies; Reactive Oxygen Species - metabolism; Reproductive system; Women; Bcl-2/Bax; Reactive oxygen species; PCNA; Neem; Nimbolide; Apoptosis
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-008-9170-z

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 IC 50 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.