A brief critical overview of the biological effects of methylglyoxal and further evaluation of a methylglyoxal-based anticancer formulation in treating cancer patients.
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.
Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata, India.
Dipa
D
Talukdar
Subhankar
S
Ray
Manju
M
Ray
Sanjoy
S
Das
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D011765:Pyruvaldehyde / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde