Melatonin decreases apoptosis in gastric mucosa during aging.

BACKGROUND AND AIMS: The aging process of tissues is usually accompanied by an increased rate of apoptosis. Although melatonin has been reported to delay aging by scavenging free radicals, its role in the aging of gastric mucosa is not known. In this study, we examined the effects of exogenous melatonin (MLT) on the caspase-dependent apoptosis of gastric mucosa during aging. METHODS: A total of 55 young, middle-aged and aged male Wistar-albino rats were used in this study. The rats were divided into control groups, treated with 0.1 mL of phosphate buffered saline (PBS) containing 1% ethanol, and melatonin groups, treated with MLT (10 mg/kg/day s.c., dissolved in 0.1 mL of PBS containing 1% ethanol) for 21 days. Plasma thiobarbituric acid (TBARS) and sulfhydryl (RSH) levels were studied as oxidant-antioxidant parameters. Caspase-3 activity of the gastric mucosal tissue was assayed as an indicator of apoptosis. The p53 protein level of the gastric mucosa was assayed using a p53 pan ELISA. RESULTS: The plasma TBARS and caspase-3 activity of the gastric mucosa were significantly increased in the aged group. MLT significantly decreased the plasma TBARS levels in all the study groups. MLT also significantly decreased the caspase-3 activity of the gastric mucosa in the aged group (p<0.001). Melatonin had no effect on the p53 expression levels of the gastric mucosa. CONCLUSIONS: In conclusion, our findings suggest that aging gastric mucosa is closely related to a higher apoptosis rate and an increase in caspase- 3 activity. Exogenous MLT might delay aging by decreasing caspase-3 activity.

Low dose chemotherapeutic drugs without overt cytotoxic effects decrease the secretion of VEGF by cultured human tumor cells: a tentative relationship between drug type and tumor cell type response.

BACKGROUND: The metronomic use of chemotherapeutic drugs is presumed to have anti-angiogenic effect. In the current study, we aimed to test the effects of lower doses of cytotoxic agents on VEGF secretion from tumor cell lines. METHODS: We tested the cytotoxic effects of widely used chemotherapeutic drugs including 5-florouracil, irinotecan, oxaliplatin, paclitaxel and docetaxel in tumor cell lines, MCF-7 (human breast cancer cell line) HT-29 (human colon cancer cell line) and a primary gastric cancer cell line and calculated the IC50 values. We've also assayed the effects of the lower doses of chemotherapeutic drugs on the levels of VEGF secreted by tumor cells in vitro. RESULTS: The human primary gastric cancer cells were more resistant to 5-FU and oxaliplatin than the HT29 and MCF-7 cell lines (p < 0.001). No significant differences were noticed in terms of the IC50 values of the irinotecan, docetaxel and paclitaxel among the studied tumor cell lines (p > 0.05). The test drugs yielded significant decreases in VEGF levels at the doses of -2 log of IC50 values in MCF-7 and primary gastric cancer cell lines. While 5-florouracil did not inhibit the VEGF secretion of HT-29 cell line, irinotecan, oxaliplatin, docetaxel and paclitaxel significantly decreased the levels of secreted VEGF. CONCLUSIONS: Our results suggest that lower doses of chemotherapeutic drugs decrease VEGF secretion from tumor cells without causing substantial cell killing. The data suggest the occurrence of a kind of selective drug-tumor cell type relationship.