2013
DOI: 10.1016/j.taap.2013.04.020
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Arsenic exposure induces the Warburg effect in cultured human cells

Abstract: Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure … Show more

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Cited by 64 publications
(53 citation statements)
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References 43 publications
(43 reference statements)
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“…We and others have found that AfB 1 preferentially, and irreparably (due to a lack of NER) damages mtDNA [15–17]. Arsenite, a global drinking water contaminant associated with the development of skin, lung, and bladder cancer, is a well-known inhibitor of several Krebs cycle dehydrogenases [48], ETC complexes [49], and is also capable of causing metabolic shifts from OXPHOS to aerobic glycolysis, otherwise known as the Warburg effect [36, 50]. Exposure to rotenone, a pesticide and prototypical mitotoxicant that acts by inhibiting complex I of the ETC leading to superoxide production, is associated with the development of Parkinson's disease [51].…”
Section: Resultsmentioning
confidence: 99%
See 2 more Smart Citations
“…We and others have found that AfB 1 preferentially, and irreparably (due to a lack of NER) damages mtDNA [15–17]. Arsenite, a global drinking water contaminant associated with the development of skin, lung, and bladder cancer, is a well-known inhibitor of several Krebs cycle dehydrogenases [48], ETC complexes [49], and is also capable of causing metabolic shifts from OXPHOS to aerobic glycolysis, otherwise known as the Warburg effect [36, 50]. Exposure to rotenone, a pesticide and prototypical mitotoxicant that acts by inhibiting complex I of the ETC leading to superoxide production, is associated with the development of Parkinson's disease [51].…”
Section: Resultsmentioning
confidence: 99%
“…Although growing evidence suggests that the mitochondrion is an important target of arsenic toxicity [36, 4850], low dose arsenic has also been linked to hormesis in which the induction of protective mechanisms is associated with therapeutic effects [76, 77]. The reported hormetic effects of arsenic include: reduced risk for non-melanoma skin cancer in Denmark [78], increased growth advantage of cells in culture [79, 80], and lifespan extension in C. elegans [79].…”
Section: Discussionmentioning
confidence: 99%
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“…Unlike normal cells which produce lactate under anaerobic conditions only, the Warburg effect states that cancer cells generate large quantities of lactate regardless of oxygen availability [202]. This study was potentially the first to link an environmental toxicant with the induction of the Warburg effect, and thus this discovery may assist in identifying the role of arsenic toxicity in other diseases associated with disrupted energy metabolism, such as diabetes and atherosclerosis [201].…”
Section: Studies Show That Hbe and Hpf Cells Generate Elevated Ros Lementioning
confidence: 86%
“…Zhao et al [201] recently discovered that long-term exposure to arsenic altered cellular energy metabolism through the induction of aerobic glycolysis (the Warburg effect), as observed in arsenite-treated HBE and other human cell lines cells. The Warburg effect is a metabolically supportive phenotype for the increased energy demands associated with the growth, proliferation and invasion of cancer cells (see the review by Vander Heiden et al [202]).…”
Section: Studies Show That Hbe and Hpf Cells Generate Elevated Ros Lementioning
confidence: 99%