Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells.

INTRODUCTION: Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE), a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in prostate cancer cells were studied for the first time. METHODS: In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis. RESULTS: Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE. CONCLUSION: Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer.

Relationship of oestrogen receptor alpha gene polymorphisms with risk for benign prostatic hyperplasia and prostate cancer in Chinese men.

The relationship of oestrogen receptor with benign prostatic hyperplasia (BPH) and prostate cancer (PC) is not clear at present. This study aimed to investigate the molecular mechanism underlying the occurrence and development of BPH and prostate.Two hundred forty-four PC cases, 260 BPH patients, and 222 healthy men were recruited from Han people in China, and the oestrogen receptor alpha (ESRα) gene polymorphism (rs2234693 [PvuII] and rs9340799 [XbaI]) on intron 1 was determined. The relationship of gene polymorphism with PC and BPH was evaluated with Logistic regression, and the linkage disequilibrium and haplotyping were assessed with SHEsis software.The risk for PC in BPH patients with PvuII C allele was higher (OR = 1.437, 95% CI: 1.110-1.859), but the differentiation degree of cancer cells was relatively better in PC patients with PvuII C allele (OR = 0.419, 95% CI: 0.285-0.616), and most of them are circumscribed (OR = 0.706, 95% CI: 0.485-1.02). There was significant linkage disequilibrium between PvuII and XbaI. The genotype TTAG not only induced BPH (OR = 6.260, 95% CI: 1.407-27.852), but increased the risk for PC (OR = 6.696, 95% CI: 1.504-29.801). However, the genotype TTAG in BPH patients had no relationship with the risk for PC (P > 0.05). Furthermore, men with haplotype TG were more likely to suffer PC (OR = 9.168, 95% CI: 2.393-35.119), but men with haplotype TA and enlarged prostate had a low risk for PC (OR = 0.708, 95% CI: 0.551-0.912).These results show the relationship between ESRα gene polymorphism and susceptibility to PC and BPH in Chinese men, and the ethnic and regional difference as well.

Evaluation of in vivo antioxidant activity of Hericium erinaceus polysaccharides.

Hericium erinaceus polysaccharide (HEP) is a traditional Chinese medicine. In the present study, chemical composition and antioxidant activity of HEP was investigated. HPLC analysis showed that the HEP was composed of xylose (7.8%), ribose (2.7%), glucose (68.4%), arabinose (11.3%), galactose (2.5%) and mannose (5.2%). HEP was pre-administered to mice by gavage at a dose of 300 mg/kg for 15 days. Results found that HEP preadministration resulted in a significant decline in blood urea nitrogen (BUN), serum creatinine (Scr) and increase in creatinine clearance (CrCI) levels in HEP-pretreated group compared to renal ischemia reperfusion (IR) group. Malondialdehyde (MDA) level significantly increased, whereas Level of reduced glutathione (GSH) markedly decreased in renal IR animals. These results indicate that IR induced renal oxidative injury damage, as indicated by a increase in MDA level, and decrease in GSH level as well as the antioxidant enzymes activity. Such effects reflect that HEP can significantly decrease lipid peroxidation level and increase antioxidant enzymes activities in experimental animals.