Kang, Joon Hee Lee, Seon-Hyeong Lee, Jae-Seon Nam, Boas Seong, Tae Wha Son, Jaekyoung Jang, Hyonchol Hong, Kyeong Man Lee, Cheolju Kim, Soo-Youl 2024-01-20T03:33:41Z 2024-01-20T03:33:41Z 2021-09-05 2016-08-02 1949-2553 https://pubs.kist.re.kr/handle/201004/123798 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. English IMPACT JOURNALS LLC CELL LUNG-CANCER LEUKEMIC HL-60 CELLS BREAST-CANCER METABOLISM GOSSYPOL DISEASE TRIAL GENE PHARMACOLOGY CARBOPLATIN Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion Article 10.18632/oncotarget.10354 1 ONCOTARGET, v.7, no.31, pp.49397 - 49410 ONCOTARGET 7 31 49397 49410 scie scopus 000385422000045 2-s2.0-84981333318 Oncology Cell Biology Oncology Cell Biology Article CELL LUNG-CANCER LEUKEMIC HL-60 CELLS BREAST-CANCER METABOLISM GOSSYPOL DISEASE TRIAL GENE PHARMACOLOGY CARBOPLATIN aldehyde dehydrogenase NSCLC gossypol phenformin cancer metabolism