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Utilizing hydrogen sulfide as a novel anti‐cancer agent by targeting cancer glycolysis and p H imbalance
Author(s) -
Lee ZW,
Teo XY,
Tay E YW,
Tan CH,
Hagen T,
Moore P K,
Deng LW
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12773
Subject(s) - cancer cell , sodium hydrosulfide , glycolysis , cancer , intracellular , intracellular ph , chemistry , viability assay , biochemistry , cell , cancer research , biology , medicine , enzyme , hydrogen sulfide , sulfur , organic chemistry
Background and Purpose Many disparate studies have reported the ambiguous role of hydrogen sulfide ( H 2 S ) in cell survival. The present study investigated the effect of H 2 S on the viability of cancer and non‐cancer cells. Experimental Approach Cancer and non‐cancer cells were exposed to H 2 S [using sodium hydrosulfide ( NaHS ) and GYY 4137] and cell viability was examined by crystal violet assay. We then examined cancer cellular glycolysis by in vitro enzymatic assays and p H regulator activity. Lastly, intracellular p H (p H i ) was determined by ratiometric p H i measurement using BCECF staining. Key Results Continuous, but not a single, exposure to H 2 S decreased cell survival more effectively in cancer cells, as compared to non‐cancer cells. Slow H 2 S ‐releasing donor, GYY 4137, significantly increased glycolysis, leading to overproduction of lactate. H 2 S also decreased anion exchanger and sodium/proton exchanger activity. The combination of increased metabolic acid production and defective p H 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. Conclusions and Implications Low and continuous exposure to H 2 S targets metabolic processes and p H homeostasis in cancer cells, potentially serving as a novel and selective anti‐cancer strategy.