Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion

Title
Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion
Authors
이철주강준희이선형이재선보아스 남성태화선재경장현철홍경만김수율
Issue Date
2016-08
Publisher
Oncotarget
Citation
VOL 7, NO 31-49410
Abstract
Among ALDH isoforms, ALDH1L1 in the folate pathway showed highly increased expression in non-small-cell lung cancer cells (NSCLC). Based on the basic mechanism of ALDH converting aldehyde to carboxylic acid with by-product NADH, we suggested that ALDH1L1 may contribute to ATP production using NADH through oxidative phosphorylation. ALDH1L1 knockdown reduced ATP production by up to 60% concomitantly with decrease of NADH in NSCLC. ALDH inhibitor, gossypol, also reduced ATP production in a dose dependent manner together with decrease of NADH level in NSCLC. A combination treatment of gossypol with phenformin, mitochondrial complex I inhibitor, synergized ATP depletion, which efficiently induced cell death. Pre-clinical xenograft model using human NSCLC demonstrated a remarkable therapeutic response to the combined treatment of gossypol and phenformin.
URI
http://pubs.kist.re.kr/handle/201004/65028
ISSN
1949-2553
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KIST Publication > Article
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