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内容記述 |
Reactive oxygen species (ROS) generated in the living body are associated with various diseases including cancer. We have developed many kinds of antioxidants derived from natural products to scavenge ROS efficiently and reported that a catechin analog, planar catechin (PCat), showed a 10-fold higher radical-scavenging activity and a remarkable cytotoxicity in cancer cells compared to the original (+)-catechin. In this study, in order to further enhance the antioxidant activity, we synthesized a PCat derivative conjugated with teprenone, PCat-Tep. Teprenone is known to show protective effects of gastric mucosa and suppression effects of oxidative stress. In this study, the effects of PCat-Tep on cells were examined.A rat gastric cancer cell line, RGK1, was treated with PCat-Tep, and the cell viability was measured by a WST assay method. The ROS scavenging activity of PCat-Tep was evaluated by electron spin resonance (ESR) measurement. DNA protection effects against X-ray irradiation were also investigated using supercoiled pBR322 plasmid DNA.PCat-Tep showed a significant cytotoxicity compared to PCat. To examine the type of cell death caused by the PCat-Tep treatment, the expressions of apoptotic marker were investigated and the number of annexin V-positive cells increased and the expression levels of cleaved caspase-3 were also elevated. On the other hand, while the ROS scavenging activity and DNA protection effects against X-ray irradiation by PCat-Tep treatment were confirmed, the effects were limited compared to the parental PCat.Teprenone conjugation with PCat enhanced cytotoxicity. However, clarification of the relationship between cytotoxicity and antioxidant activity needs further investigation. |
