Topic
Aldehyde dehydrogenase
About: Aldehyde dehydrogenase is a research topic. Over the lifetime, 3365 publications have been published within this topic receiving 107683 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: It is shown that bromodomain and extraterminal (BET) inhibitors suppress ALDH activity by abrogating BRD4-mediated ALDH1A1 expression through a super-enhancer element and its associated enhancer RNA.
Abstract: The emergence of tumor cells with certain stem-like characteristics, such as high aldehyde dehydrogenase (ALDH) activity due to ALDH1A1 expression, contributes to chemotherapy resistance and tumor relapse. However, clinically applicable inhibitors of ALDH activity have not been reported. There is evidence to suggest that epigenetic regulation of stem-related genes contributes to chemotherapy efficacy. Here, we show that bromodomain and extraterminal (BET) inhibitors suppress ALDH activity by abrogating BRD4-mediated ALDH1A1 expression through a super-enhancer element and its associated enhancer RNA. The clinically applicable small-molecule BET inhibitor JQ1 suppressed the outgrowth of cisplatin-treated ovarian cancer cells both in vitro and in vivo Combination of JQ1 and cisplatin improved the survival of ovarian cancer-bearing mice in an orthotopic model. These phenotypes correlate with inhibition of ALDH1A1 expression through a super-enhancer element and other stem-related genes in promoter regions bound by BRD4. Thus, targeting the BET protein BRD4 using clinically applicable small-molecule inhibitors, such as JQ1, is a promising strategy for targeting ALDH activity in epithelial ovarian cancer. Cancer Res; 76(21); 6320-30. ©2016 AACR.
108 citations
TL;DR: The stomach may contribute only a small portion of the alcohol metabolism observed in humans, and the liver may be the major site for first-pass metabolism, suggesting that different vulnerabilities to ethanol-induced mucosal injury may exist.
108 citations
TL;DR: Evidence for several newly identified antioxidant-inducible genes is presented, the proposed mechanisms of antioxidant signal transduction leading to enhanced expression of these enzymes are described, and the mechanisms and consequences of induction of phase 2 xenobiotic-metabolizing enzymes by antioxidants are described.
Abstract: Publisher Summary Antioxidants inhibit the propagation of free radical reactions Because of their widespread use as preservatives in processed foods, their biochemical effects have been investigated Early feeding studies indicated that butylated hydroxytoluene (BHT) increased liver weight, induced proliferation of smooth endoplasmic reticulum, and elevated several hepatic microsomal mono-oxygenase activities typical of phase 1 metabolism In addition to phase1, antioxidants also induce phase2 xenobiotic-metabolizing enzymes Phase2 enzymes detoxify activated electrophilic metabolites of xenobiotics via conjugation of endogenous substrates such as glutathione (GSH) Antioxidants act to directly terminate the propagation of free radical reactions, and increase the activity of enzymes those readily metabolize and aid in the elimination of potential cytotoxic chemicals Dietary administration of antioxidants induced phase 2 xenobiotic-metabolizing enzymes Induction of phase 2 enzymes by antioxidants was found in many organs and tissues, such as liver, lung, kidney, small intestine, colon, and spleen, thereby affording protection at many anatomical sites This chapter presents evidence for several newly identified antioxidant-inducible genes, describes the proposed mechanisms of antioxidant signal transduction leading to enhanced expression of these enzymes, and complements the information presented in related reviews concerning the mechanisms and consequences of induction of phase 2 xenobiotic-metabolizing enzymes by antioxidants The chapter discusses the genes induced by antioxidants—cytochrome P450s, Glutathione, S-transferases, NAD(P)H: quinone reductase, UDP-glucuronosyltransferases, microsomal epoxide hydrolase, aflatoxin BI-aldehyde reductase, dihydrodiol dehydrogenases, aldehyde dehydrogenases, enzymes of glutathione and reduced nicotinamide metabolism, and other proteins and enzymes The chapter delves into the mechanisms of gene induction by antioxidants—the antioxidant-response element (ARE), proteins binding and signal transduction through the ARE—and the consequences of antioxidant gene induction The regulation of antioxidant-inducible genes helps understand the signals leading to cellular transformation and carcinogenesis Antioxidants can be used to decipher the encrypted signal transduction pathways that prevent cell transformation and carcinogenesis
108 citations
TL;DR: In many malignancies, most notably in breast cancer, ALDH activity and expression appears to be a promising marker and potential therapeutic target for treating metastasis in the clinical setting.
Abstract: There is accumulating evidence indicating that aldehyde dehydrogenase (ALDH) activity selects for cancer cells with increased aggressiveness, capacity for sustained proliferation, and plasticity in primary tumors. However, emerging data also suggests an important mechanistic role for the ALDH family of isoenzymes in the metastatic activity of tumor cells. Recent studies indicate that ALDH correlates with either increased or decreased metastatic capacity in a cellular context-dependent manner. Importantly, it appears that different ALDH isoforms support increased metastatic capacity in different tumor types. This review assesses the potential of ALDH as biological marker and mechanistic mediator of metastasis in solid tumors. In many malignancies, most notably in breast cancer, ALDH activity and expression appears to be a promising marker and potential therapeutic target for treating metastasis in the clinical setting.
107 citations
TL;DR: The data indicate that the rat nasal mucosa, which is the major target site for both aldehydes in inhalation toxicity studies, can metabolize both formaldehyde and acetaldehyde, and that the specific activities of formalde and aldehyde dehydrogenase in homogenates of the nasal mucoso are essentially unchanged following repeated exposures to toxic concentrations of either compound.
107 citations