Clinical physiology and pharmacology of GSTZ1/MAAI

Stacpoole, Peter W.

doi:10.1016/j.bcp.2023.115818

Cited by 3 publications

(3 citation statements)

References 92 publications

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“…The lower panel shows its metabolization to glyoxylate by the enzyme glutathione transferase zeta 1 (GSTZ1), also known as maleylacetoacetate isomerase (MAAI). GSTZ1 dechlorinates DCA and GSTZ1 genetic variations influence the metabolic rate of DCA processing [ 75 ]. Glyoxylate is oxidized to oxalate, which is excreted in the urine.…”

Section: Figurementioning

confidence: 99%

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Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Pharmaceuticals

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Rarely has a chemical elicited as much controversy as dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product, then a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects on experimental animals. These publications showed contradictory results in vivo and in vitro such that a thorough consideration of this compound’s in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and health authorities’ approval, DCA has been introduced in off-label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are few thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA’s benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in it.

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Section: Figurementioning

confidence: 99%

“…The best known and main mechanism of action of DCA seems to be the inhibition of pyruvate dehydrogenase kinase (PDK) and its isoforms [ 71 , 75 , 77 , 78 , 82 , 89 ]. This inhibition increases the flux of pyruvate into the mitochondria, promoting glucose oxidation instead of glycolysis [ 90 ].…”

Section: Introductionmentioning

confidence: 99%

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…It is a halogenated carboxylic acid and a structural analog of pyruvate.Lower panel shows its metabolization to glyoxylate by the enzyme glutathione transferase zeta 1 (GSTZ1) also known as maleylacetoacetate isomerase (MAAI). GSTZ1 dechlorinates DCA and GSTZ1 genetic variations influence the metabolic rate of DCA processing[75]. Glyoxylate is oxidized to oxalate which is excreted by the urine.…”

mentioning

confidence: 99%

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Preprint

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Rarely has a chemical elicited as much controversy as has dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product. Then it was a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects in experimental animals. These publications showed contradictory results in vivo and in vitro, so that a thorough consideration of this compound in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and lack of health authorities’ approval, DCA has been introduced in off -label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are limited thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in oncology treatment.

show abstract

Glutathione Transferases

Mannervik,

Morgenstern

2024

Reference Module in Biomedical Sciences

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Clinical physiology and pharmacology of GSTZ1/MAAI

Cited by 3 publications

References 92 publications

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Glutathione Transferases

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