Distinct Cellular Calcium Metabolism in Radiation-sensitive RKO Human Colorectal Cancer Cells

Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive Ca(2+) release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of Ca(2+) homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular Ca(2+) metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (γ)-irradiation. In irradiated RKO cells, Ca(2+) influx via activation of NCX reverse mode was enhanced and a decline of [Ca(2+)]i via forward mode was accelerated. The amount of Ca(2+) released from the ER in RKO cells by the activation of IP3 receptor was also enhanced by irradiation. An increase in [Ca(2+)]i via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that γ-irradiation elicits enhancement of cellular Ca(2+) metabolism in radiation-sensitive RKO cells yielding programmed cell death.