SDHA-mediated Warburg effect in malignantly transformed human bronchial epithelial cells following long-term exposure to radon.

Abstract

Radon and its progeny have been classified as human class I carcinogens by the IARC. However, the mechanisms by which radon induces lung and other cancers, especially the radon-induced Warburg effect, have not been fully elucidated. The aim of this study was to investigate the role of the succinate dehydrogenase subunit A (SDHA)-mediated Warburg effect in (human bronchial epithelial) BEAS-2B cells with malignant transformations induced by long-term radon exposure. Soft agar colony formation and MMP-9 were increased following radon-induced malignant transformation. Additionally, we observed the Warburg effect in BEAS-2B cells following long-term radon exposure, evidenced by increases in the levels of glucose uptake, lactate, and lactate dehydrogenase (LDH). Following radon exposure, the expression of SDHA was decreased, while the levels of HIF-1α and hexokinase-2 (HK2) were increased. Our findings suggested that the SDHA-associated pathway may be involved in mediating the Warburg effect in radon-induced malignant transformation of BEAS-2B.