Down-regulation of cobalt-induced HIF-1α expression correlates with cell proliferation and apoptosis in human gastric carcinoma cells

Previously we reported that the hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression correlated with cell proliferation and apoptosis under 500 mM of CoCl2 treatment in a human gastric carcinoma cell line, MKN-1. Herein we report a similar correlation in other cell lines, MKN-45 and TMK-1. The dual-phase expression of HIF-1 alpha was highest at 6 and 8 h of treatment in MKN-45 and TMK-1, respectively, while the peak in MKN-1 occurred at 4 h. The cell viability indices showed a similar dual phase to the HIF-1 alpha expression, while the apoptotic indices started to increase as the level of the HIF-1 alpha expression decreased. In our previous study, the FACS analysis showed a marked G(2)/M arrest and an increase of the pre-G(1) area in MKN-1 after 36 h of treatment, whereas the G(2)/M arrest was not observed in MKN-45 and TMK-1. The expression of cell cycle and apoptosis-related proteins showed a correlation with the HIF-1 alpha expression and the FACS results, which suggested that the level of HIF-1 alpha correlated with proliferation and apoptosis in human gastric carcinoma cell lines with a possible cell-type specific pattern.