Abstract 209: The effect of heme influx on initiation and tumorigenesis of NSCLC

Abstract

Abstract Heme is a central molecule for mitochondrial function and for all processes involved in oxygen utilization. Heme serves as a prosthetic group or as a cofactor for a number of oxidative phosphorylation enzymes and other oxygen-utilizing hemoproteins. Heme also directly regulates the synthesis, translocation and assembly of these enzyme complexes. Most, if not all, human cells can synthesize and uptake heme from the circulation. A number of epidemiological studies have shown that high heme intake is associated with increased risk of cancer, including lung cancer. Recent studies carried out in our lab showed intensified mitochondrial respiration and increased levels of heme and hemoproteins in non-small-cell lung cancer (NSCLC) cells. Together, these experimental and epidemiological studies strongly suggest that heme is an “oncometabolite.” To assess the status of heme metabolism in cancer cells, we performed a series of experiments in NSCLC cells and compared the results with an immortalized normal lung cell line, HBEC30KT. We used Zinc protoporphyrin, an analogue of heme to measure the level of heme uptake. We found that heme uptake as well as heme synthesis are significantly elevated in all NSCLC cells compared to HBEC. The rate of heme degradation was also measured in these cell lines. Previously, our lab demonstrated that lowering intracellular heme levels selectively decreases oxygen consumption in NSCLC cells and inhibits cell migration and colony formation. Experiments are underway to test ways to alter intracellular heme availability and characterize their effects on NSCLC tumor growth and metastasis. Citation Format: Sagar Sohoni, Md Maksudul Alam, Chantal Vidal, Jagmohan Hooda, Li Zhang. The effect of heme influx on initiation and tumorigenesis of NSCLC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 209.