Utilizing hydrogen sulfide as a novel anti‐cancer agent by targeting cancer glycolysis and pH imbalance. (2nd July 2014)

• Record Type: Journal Article
• Authors: Lee, Z‐W; Teo, X‐Y; Tay, E Y‐W; Tan, C‐H; Hagen, T; Moore, P K; Deng, L‐W
• Is Part Of: British journal of pharmacology. Volume 171:Number 18(2014:Sep.)
• Page Start: 4322
• Page End: 4336
• Publication Date: 2014-07-02
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12773
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12773-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Many disparate studies have reported the ambiguous role of hydrogen sulfide (H<sub>2</sub>S) in cell survival. The present study investigated the effect of H<sub>2</sub>S on the viability of cancer and non‐cancer cells.</p> </sec> <sec id="bph12773-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>Cancer and non‐cancer cells were exposed to H<sub>2</sub>S [using sodium hydrosulfide (NaHS) and GYY4137] and cell viability was examined by crystal violet assay. We then examined cancer cellular glycolysis by <italic>in vitro</italic> enzymatic assays and pH regulator activity. Lastly, intracellular pH (pH<sub>i</sub>) was determined by ratiometric pH<sub>i</sub> measurement using BCECF staining.</p> </sec> <sec id="bph12773-sec-0003" sec-type="section"> <title>Key Results</title> <p>Continuous, but not a single, exposure to H<sub>2</sub>S decreased cell survival more effectively in cancer cells, as compared to non‐cancer cells. Slow H<sub>2</sub>S‐releasing donor, GYY4137, significantly increased glycolysis, leading to overproduction of lactate. H<sub>2</sub>S also decreased anion exchanger and sodium/proton exchanger activity. The combination of increased metabolic acid production and defective pH regulation resulted in an uncontrolled intracellular acidification, leading to cancer cell death. In contrast, no significant intracellular acidification or cell death was observed in non‐cancer cells.</p> </sec> <sec id="bph12773-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>Low and continuous exposure to H<sub>2</sub>S targets metabolic processes and pH homeostasis in cancer cells, potentially serving as a novel and selective anti‐cancer strategy.</p> </sec> </abstract>