Nimbolide inhibits androgen independent prostate cancer cells survival and proliferation by modulating multiple pro-survival signaling pathways.
BACKGROUND
Prostate cancer is the most prominent cancer in men, experiencing a relapse in disease often express high serum TNF-α levels. It has been correlated with increased cell survival and proliferation of prostate cancer cells. Previous studies reported that nimbolide, a terpenoid derived from the leaves and flowers of neem tree inhibits cancer growth through selective modulation of cell signaling pathways linked to inflammation, survival, proliferation, angiogenesis and metastasis.


METHODS
The present study aimed to examine the effect of nimbolide at 1 and 2μM concentrations on TNF-α/TNFR1 mediated signaling molecules involved in cell survival and proliferation in PC-3 cell line via NF-κB and MAPK pathways by real time PCR and western blot. Protein and compound interaction were performed by Molecular docking analysis.


RESULTS
Our results indicate that nimbolide treatment suppressed expression of TNF-α, SODD, Grb2, SOS mRNA and modulated TNF-α/TNFR1 regulated NF-κB and MAPK signaling molecules in PC-3 cells. Additional molecular dynamics simulation studies confirmed the stability of nimbolide and signaling molecules binding interactions. Binding pose analysis revealed the significance of hydrogen bond interactions for effective stabilization of virtual ligand protein complexes.


CONCLUSION
Nimbolide inhibited prostate cancer cell survival and proliferation via NF-κB and MAPK pathways.
['Singh|P Raja|PR|', 'Priya|E Sugantha|ES|', 'Balakrishnan|S|S|', 'Arunkumar|R|R|', 'Sharmila|G|G|', 'Rajalakshmi|M|M|', 'Arunakaran|J|J|']
D000728:Androgens D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D015972:Gene Expression Regulation, Neoplastic D006801:Humans D036701:Limonins D020935:MAP Kinase Signaling System D008297:Male D062105:Molecular Docking Simulation D000072000:NF-KappaB Inhibitor alpha D016328:NF-kappa B D009363:Neoplasm Proteins D011471:Prostatic Neoplasms D012333:RNA, Messenger D047888:Receptors, Tumor Necrosis Factor, Type I D015398:Signal Transduction D014409:Tumor Necrosis Factor-alpha
Nimbolide Prostate cancer Cell survival and proliferation TNF-α TNFR1 NF-κB and MAPK pathway Docking