7-H-Pyrrolo[2,3-d]pyrimidine derivative acts as promising agent for gastric cancer treatment by inducing cell death
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In the present study effect of 7-H-pyrrolo[2,3-d]pyrimidine derivative (7-HPPD) on viability of MKN28 and MKN74 gastric cancer cells was investigated. There was no significant change in GES-1 cell viability on treatment with 7-HPPD for 48 h. MKN28 and MKN74 cell viability was reduced to 21 and 23%, respectively, on treatment with 7-HPPD at concentration of 50 µM. Hoechst 33342 staining showed that the cells treated with 7-HPPD showed condensation of chromatin material, presence of apoptotic bodies and intense blue fluorescence. Treatment of MKN28 and MKN74 cells with 7-HPPD markedly increased the release of LDH. Z-VAD-FMK prevented 7-HPPD-induced suppression of MKN28 and MKN74 cell viability. Exposure to 15, 20, 25, 30 and 50 µM concentrations of 7-HPPD caused concentration-based increase in caspase-8, -9, -3 and cleaved PARP. A significant increase in ROS production was caused by 7-HPPD in MKN28 and MKN74 cells. Increasing the concentration of 7-HPPD from 10 to 50 µM did not increase the expression of RIP3 protein. In summary, 7-HPPD suppresses gastric cancer cell growth by inducing apoptosis through increase in caspase expression and ROS production. Consequently, 7-HPPD may be used for the development of treatment strategy for gastric cancer.
KeywordsCaspase Necroptosis Autophagy Chromatin condensation
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