AUTHOR=Petronek Michael S. , Bayanbold Khaliunaa , Amegble Koffi , Tomanek-Chalkley Ann M. , Allen Bryan G. , Spitz Douglas R. , Bailey Charvann K. 

TITLE=Evaluating the iron chelator function of sirtinol in non-small cell lung cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1185715

DOI=10.3389/fonc.2023.1185715

ISSN=2234-943X

ABSTRACT=Sirtinol is an inhibitor of both SIRT1 and 2; however, it also functions as a tridentate iron chelator by binding Fe3+ with 3:1 stoichiometry. The biological consequences of this function remain unexplored. Consistent with preliminary literature, we show that sirtinol can deplete intracellular labile iron pools in both A549 and H1299 non-small cell lung cancer cells acutely. Interestingly, a temporal adaptive response occurs in A549 cells as sirtinol enhances transferrin receptor stability and represses ferritin heavy chain translation through impaired aconitase activity and apparent IRP1 activation. This effect was not observed in H1299 cells. Holo-transferrin supplementation significantly enhanced colony formation in A549 cells while increasing sirtinol toxicity. This effect was not observed in H1299 cells. Thus, the chelator function of sirtinol is a meaningful drug effect that warrants further consideration.