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Gastric cancer depends on aldehyde dehydrogenase 3A1 for fatty acid oxidation.

ABSTRACT: The major source of ATP in cancer cells remains unclear. Here, we examined energy metabolism in gastric cancer cells and found increased fatty acid oxidation and increased expression of ALDH3A1. Metabolic analysis showed that lipid peroxidation by reactive oxygen species led to spontaneous production of 4-hydroxynonenal, which was converted to fatty acids with NADH production by ALDH3A1, resulting in further fatty acid oxidation. Inhibition of ALDH3A1 by knock down using siRNA of ALDH3A1 resulted in significantly reduced ATP production by cancer cells, leading to apoptosis. Oxidative phosphorylation by mitochondria in gastric cancer cells was driven by NADH supplied via fatty acid oxidation. Therefore, blockade of ALDH3A1 together with mitochondrial complex I using gossypol and phenformin led to significant therapeutic effects in a preclinical gastric cancer model.

SUBMITTER: Lee JS

PROVIDER: S-EPMC6841934 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Gastric cancer depends on aldehyde dehydrogenase 3A1 for fatty acid oxidation.

Lee Jae-Seon JS Kim Seung Hwa SH Lee Soohyun S Kang Joon Hee JH Lee Seon-Hyeong SH Cheong Jae-Ho JH Kim Soo-Youl SY

Scientific reports 20191108 1

The major source of ATP in cancer cells remains unclear. Here, we examined energy metabolism in gastric cancer cells and found increased fatty acid oxidation and increased expression of ALDH3A1. Metabolic analysis showed that lipid peroxidation by reactive oxygen species led to spontaneous production of 4-hydroxynonenal, which was converted to fatty acids with NADH production by ALDH3A1, resulting in further fatty acid oxidation. Inhibition of ALDH3A1 by knock down using siRNA of ALDH3A1 resulte ...[more]

PMID: 31705020

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