A Brief Critical Overview of the Biological Effects of Methylglyoxal and Further Evaluation of a Methylglyoxal-Based Anticancer Formulation in Treating Cancer Patients

Abstract

A historical perspective on methylglyoxal research is briefly presented, mentioning the documented anticancer and antiviral effects of methylglyoxal. The idea and the supporting experimental evidence of Albert Szent-Györgyi et al. that methylglyoxal is a natural growth regulator and can act as an anticancer agent are mentioned. Previously a few in vivo studies suggested safe administration of methylglyoxal. However, recent literature abounds with the toxic effects of methylglyoxal. The authors present a brief critical overview of studies indicating both toxic and beneficial effects of methylglyoxal and suggest that the beneficial effects of methylglyoxal outweigh its toxic effects. Encouraged by the studies of Szent-Györgyi et al., the present authors undertook systematic investigations to understand the mechanism of the anticancer effect of methylglyoxal. The results of these investigations led to the proposal that the fundamental changes in malignant cells are critical alterations of glyceraldehyde-3-phosphate dehydrogenase and mitochondrial complex I, and methylglyoxal's anticancer effect might be mediated by acting on these altered sites. Moreover, a new hypothesis on cancer has been proposed, suggesting that excessive ATP formation in cells may lead to malignancy. Toxicity and pharmacokinetic studies were performed on animals and it was observed that methylglyoxal is potentially safe for humans. A methylglyoxal-based anticancer formulation was developed and a three-phase study of treating a total number of 86 cancer patients was carried out. The results appear to be promising. Most of the cancer patients benefited greatly and a significant number of patients became free of the disease. Contrary to the effect of existing anticancer drugs, this methylglyoxal-based formulation is devoid of any toxic effect and reasonably effective against a wide variety of cancers. The symptomatic improvements of the many patients who died of progressive disease suggest that the formulation could also be used for palliation. The authors urge the scientific community to test the formulation and if found effective then to improve it further.

Antioxidant-rich leaf extract ofBarringtonia racemosasignificantly alters thein vitroexpression of genes encoding enzymes that are involved in methylglyoxal degradation III

“…Methylglyoxal has also been found to inactivate glyceraldehyde-3-phosphate dehydrogenase (GA3PD), a key enzyme of the glycolytic pathway, and this inactivation is responsible to a significant extent for the inhibition of glycolysis of tumor cells by methylglyoxal (Halder, Ray & Ray, 1993). These findings paved the way for anticancer drug development using methylglyoxal as a key component (Talukdar et al, 2008). Data on the toxicity effects of methylglyoxal in animal studies are however inconsistent (Kalapos, 1999).…”

The Role of Methylglyoxal-Modified Proteins in Gastric Ulcer Healing

“…For example, methylglyoxal selectively inhibits mitochondrial respiration and glycolysis in cells [56,57]. It inactivates membrane ATPases and glyceraldehyde-3-phosphate dehydrogenase, a key enzyme of the glycolytic pathway [58,59]. Recently, we have demonstrated that methylglyoxal's posttranslational modification of heat shock protein 27 (HSP27) may play an important role in cell survival in gastrointestinal cancer [60].…”

Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

“…11 These findings paved the way for anticancer drug development using MG as a key component. 12,13 A major problem with using MG as an anticancer drug is that MG, being a normal metabolite, is rapidly degraded by various enzymes present in the body. 6,14,15 Hence, shielding MG with convenient nanoparticles may prevent this in vivo degradation, making it more competent as an anticancer drug.…”