138 - Reactive oxygen species derived from mitochondria increase non-heme iron incorporation in gastric cancer cells by regulating the expression of transporters

Abstract

Iron is an essential substance for human and play many important roles such as transportation of oxygen and synthesis of DNA. However, the concentration of iron in body is strictly regulated because excess iron causes reactive oxygen species (ROS) and damages cells. Most of iron in body classified as follows: heme iron and non-heme iron. We previously reported that high level ROS derived from mitochondria (mitROS) in cancer cells enhanced the expression of heme iron transporter. In this study, we examined the relationship between non-heme iron transportation and mitROS. We used a rat gastric normal, cancer and manganese superoxide dismutase (MnSOD)-overexpressing cancer cell line, in which mitROS are specifically scavenged. Among these cell lines, non-heme iron incorporation was compared using radioactive iron compound. The incorporation in cancer cells was greater than in normal cells and decreased by overexpressing MnSOD. We also studied the expression of transporters which was related to incorporation and excretion of non-heme iron. The expression of incorporation protein DMT1 in cancer cells was greater than in normal and MnSOD-overexpressing cancer cells. On the other hand, excretion protein ferroportin decreased in cancer compared to MnSOD-overexpressing cancer cells. Thus, we concluded that cancer cellular ROS from mitochondria regulated the incorporation and excretion of non-heme iron via expression of iron transport protein.