Aldehyde dehydrogenase is used by cancer cells for energy metabolism

Abstract

We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid. We hypothesized that the NADH produced by ALDH may be a reliable energy source for ATP production in NSCLC. This study revealed that NADH production by ALDH contributes significantly to ATP production in NSCLC. Furthermore, gossypol, a pan-ALDH inhibitor, markedly reduced the level of ATP. Gossypol combined with phenformin synergistically reduced the ATP levels, which efficiently induced cell death following cell cycle arrest.

Quantification of protein markers monitoring the pre‐analytical effect of blood storage time before plasma isolation using 15N metabolically labeled recombinant proteins

“…The other 13 proteins were relatively quantified by normalizing their MRM peak area against a geometric mean of MRM peak areas of the two standard proteins . The normalized peak area was calculated as follows: where was normalized peak area of transition i in sample s , and PA i , s , STD 1, s , and STD 2, s were raw peak areas of transition i and two transitions for standard proteins in sample s …”

“…where PA i;s ⌣ was normalized peak area of transition i in sample s, and PA i, s , STD 1, s , and STD 2, s were raw peak areas of transition i and two transitions for standard proteins in sample s. 21…”

NAD- and NADPH-Contributing Enzymes as Therapeutic Targets in Cancer: An Overview

“…This enzyme converts all-trans-retinal into retinoic acid [119,121,122]. ALDH catalytic reactions produce vast amount of cytosolic NADH as the source of ATP generation in cancers [123]. ALDH1A3 also plays a role in generating acetic acid from acetaldehyde in glycolysis and gluconeogenesis as well as metabolizing amino acids, exogenous chemical substances via cytochrome P450 and lipid peroxidase product [119,121].…”

Cancer‐Cell‐Specific Drug Delivery by a Tumor‐Homing CPP‐Gossypol Conjugate Employing a Tracelessly Cleavable Linker

“…[12,13] Its antiproliferative effecti sc aused by regulating cyclineD 1, [14] autophagy, [15] and inhibition of aldehyded ehydrogenase. [16] Furthermore Gossypol is studied for combination therapy in addition with other therapeutic agentsa gainst glioblastoma, [17] pancreatic cancer cells [18] and non-small-cell lung carcinoma. [19] It has also shown cytotoxicity against breast cancer cells by inhibitingt he expression of mouse double minute 2( MDM2)a nd vascular endothelial growth factor (VEGF).…”