Abstract 386: Heme function in promoting tumorigenic potential of lung cancer cells

Heme, also known as iron protoporphyrin IX, is an essential molecule for living organisms. Heme serves as a prosthetic group in enzymes, and acts as a signaling molecule in diverse cellular processes. Mammalian cells can synthesize heme endogenously, or they can import heme from circulation via heme transporters. The synthesis of heme is carried out by eight enzymes, the first of which is the rate-limiting enzyme 5-aminolevulinate (ALA) synthase. Heme can also be transported intracellularly by transporters, such as HCP1 (heme carrier protein 1) and HRG1 (heme responsive gene 1). Finally, levels of heme are also maintained by the degrading enzyme, heme oxygenase-1 (HO-1). HO-1 is localized to the endoplasmic reticulum and is the rate-limiting enzyme in the catabolism of heme. HO-1 cleaves heme to biliverdin and carbon monoxide. Biliverdin is converted to bilirubin, which is an antioxidant and scavenger of ROS. Heme also serves as a catalytic site for various proteins that are involved in aerobic metabolism, such as respiratory chain cytochromes. For example, complex II, III, and IV of the mitochondria require heme for proper function. Importantly, epidemiologic studies have shown the association of dietary heme intake, mainly from red meat, with different cancers, including lung cancer. Therefore, we have analyzed the levels of heme synthesis, uptake, degradation, oxygen consumption and mitochondrial proteins in an immortalized, nontumorigenic human bronchial epithelial cell line (NL20) compared to the tumorigenic counterpart (NL20-TA). These studies showed that the tumorigenic cell line expressed significantly higher levels of heme flux compared to the nontumorigenic cell line. This led us to alter heme availability by overexpressing the rate-limiting enzyme of heme synthesis as well as the rate-limiting enzyme of heme degradation. Experiments are under way to characterize their effects on tumor growth and metastasis. Citation Format: Chantal Vidal, Sagar Sohoni, Li Zhang. Heme function in promoting tumorigenic potential of lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 386.