Molecular mechanism of inhibitory effects of melatonin on prostate cancer cell proliferation, migration and invasion.

The increasing incidence of prostate cancer (PCa) indicates an urgent need for the development of new effective drug therapy. There are limited options to treat the PCa, this study tried to determine a new therapy option for this acute cancer. Androgen-independent PCa cell lines PC3 and DU145 were treated with different melatonin concentrations (0.1~3.5 mM) for 1~3 days and assessed cell migration, cell invasion, cycle arrest in G0/G1 phase as well as apoptosis. We utilized RNA-seq technology to analyze the transcriptional misregulation pathways in DU145 prostate cancer cell line with melatonin (0.5 mM) treatment. Data revealed 20031 genes were up and down-regulated, there were 271 genes that differentially expressed: 97 up-regulated (P<0.05) and 174 down-regulated (P<0.05) genes. Furthermore, RNA-seq results manifested that the melatonin treatment led to a significant increase in the expression levels of HPGD, IL2Rß, NGFR, however, IGFBP3 and IL6 (P <0.05) had decreased expression levels. The immunoblot assay revealed the expression of IL2Rß and NGFR genes was up-regulated, qPCR confirmed the gene expression of HPGD and IL2RB were also up-regulated in Du145 cells. Consequently, we probed mechanisms that generate kinetic patterns of NF-κB-dependent gene expression in PCa cells responding to a NF-κB-activation, the significant results were indicated by the inhibition of the NF-kB pathway via IL2Rß actions. Based on our investigation, it could be concluded that melatonin is a chemotherapeutic molecule against PCa and provides a new idea for clinical therapy of PCa.

Anti-oxidant and Antiproliferative Activities of Mongolian Medicinal Plant Extracts and Structure Isolation of Gnetin-H Compound.

BACKGROUND: Reactive oxygen species are involved in the etiology and progress of many kinds of diseases such as cancer, cardiovascular diseases, inflammatory and neurodegenerative disorders. Epidemiological studies reported that fruits, vegetables, and wines containing a high percentage of phenolics and flavonoids showed a positive impact in treating inflammatory diseases, reducing cancer risk, and increasing life expectancy. OBJECTIVE: Some Mongolian medicinal plants were studied for their antioxidant activity and anticancer effects. METHODS: Selected Mongolian medicinal plant extracts were examined for their antioxidant activity by the DPPH-radical scavenging assay, the content of phenolics and flavonoids by Folin-Ciocalteu and the Dowd method, respectively, and anti-cancer activities in human hepatoma cell line HepG2 cells by MTT assay. RESULTS: Methanol extract from Hippophae rhamnoides L. leaf and ethanol extract from Artemisia macrocephala Jacq. ex Bess. showed the highest efficiency to scavenge free radicals. Ethanol extracts from Hippophae rhamnoides L. grain and Paeonio anomala L. leaf showed the highest total phenolics content, whereas Hippophae rhamnoides L. fruit methanol extract and ethanol extract from Caragana leucophloea pojark. mentioned the highest flavonoids content. The Artemisia macrocephala Jacq. ex Bess seed wallet and Paeonia anomala L. seed wallet showed the most potent antiproliferative effects against human liver cancer HepG2 cell line. Gnetin-H compound was isolated from the Paeonio anomala L. seed wallet extract, and its molecular structure was determined by 1H and 13C NMR spectrum and IR spectroscopy methods. CONCLUSION: The screening study on anti-oxidative effects of 21 extracts from 15 Mongolian medicinal plants showed anti-oxidative activities and was rich in phenolics and flavonoids. Among these, methanol extract of the Hippophae rhamnoides L. leaf showed a better anti-oxidative effect than the ethanol extract. Artemisia macrocephala Jacq. ex Bess and Paeonia anomala L. seed wallet mentioned the best anti-cancer effects. Gnetin-H, methyl gallate, ethylgallate were the major components in the extract from the Paeonio anomala L. seed wallet. Finally, the molecular structure of gnetin-H was determined by NMR and IR spectroscopy. Further investigation, especially in vivo antioxidant activity, is needed to justify the use of a natural source of antioxidants to prevent the progression of diseases such as cancer.