Triptolide Inhibits the Proliferation of Prostate Cancer Cells and Down-Regulates SUMO-Specific Protease 1 Expression

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa

Antioxidant Activities of Hydroalcoholic Extract of Ocimum sanctum Against Cadmium Induced Toxicity in Rats

The present study was undertaken to analyze the antioxidant (both enzymic and nonenzymic) activities of leaves of Ocimum sanctum hydroalcoholic extract against cadmium induced damage in albino rats. Oral administration of cadmium as CdCl2 (6.0 mg/kg body weight) led to significant elevation of lipid peroxidation (LPO) levels and significantly decreased Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx), Reduced Glutathione (GSH) and Vitamin C (Ascorbate) levels. Administration of Ocimum sanctum extract (100 mg/kg body weight, po) and (200 mg/kg body weight, po) before and after cadmium intoxication showed a significant decrease in LPO levels and significant increase in SOD, CAT, GPx, GSH and Ascorbate levels. The results suggest that oral administration of Ocimum sanctum extract provides significant protection against cadmium induced toxicity in Wistar albino rats