Prostate cancer, a multifocal disease, is initially responsive to therapies that inhibit androgen receptor (AR) signaling, but the disease eventually progresses to an androgen-independent or refractory state. Understanding and modulating AR function may be essential to the development of new treatment modalities. Native to the Indian subcontinent, the Azadirachta indica plant (Neem) possesses potent anticarcinogenic properties. Nimbolide is a bioactive constituent of the Neem leaves. Previous studies reveal that nimbolide inhibits androgen-independent prostate cancer cells survival and proliferation by modulating multiple pro-survival signaling pathways. In this study, we examined the effects of nimbolide on the cell growth of LNCaP human prostate cancer cells, an advanced and androgen-sensitive cell line. LNCaP cells were treated with different concentrations of nimbolide for 24-72 hours. Cell proliferation was dose-dependently inhibited at 1, 2, 5, 10 µM nimbolide with more than 50% growth inhibitory effects between 1 and 2 µM. Preliminary data suggest that nimbolide may exhibit anti-proliferative activity in androgen-dependent prostate cancer cells, and the progression of prostate cancer to metastatic or advanced disease may occur by modulating the AR signaling pathway.
