Online citations, reference lists, and bibliographies.

Carcinostatic Activity Of Methylglyoxal And Related Substances In Tumour-bearing Mice.

Jr. Peter V. Conroy
Published 1978 · Biology, Medicine
Cite This
Download PDF
Analyze on Scholarcy
Share
Methylglyoxal treatment of tumour cells in vitro primarily depresses protein synthesis, in contrast to trans-4-hydroxypent-2-enal (HPE) which preferentially inhibits DNA synthesis. Methylglyoxal and hpe are potent carcinostatic agents in vitro but relatively ineffective in vivo. Both aldehydes have a short half-life in vivo which may explain their poor carcinostatic properties when administered other than peritumorally. Several possibilities of increasing the effective half-life were investigated including (i) multiple intraperitoneal injections, (ii) concomitant administration of an inhibitor of glyoxalase I, (iii) administration of aldehyde-cysteine adducts, and (iv continuous intravenous infusion. Methylglyoxal (36 mg/kg i.p., twice daily) was slightly less effective in inhibiting the growth of the solid form of Ehrlich carcinoma than a dose of 72 mg/kg (inj. 1); 36 mg/kg (inj. 2) 46.2% compared to 51%. The aldehyde was more effective aginst the ascitic form of the tumour, with 99.76% inhibition of growth after giving 72 mg/kg twice daily for five days followed by 36 mg/kg for five days. The glyoxalase I inhibitor S-(p-bromobenzyl)-glutathione didnot significantly enhance the activity of methylglyoxal against the solid form of the tumour. Nicotinamide (1% w/v in the drink) was similarily inactive. Methylglyoxal in combination with nicotinamide was significantly more effect (P less than 0.05) than methylglyoxal alone (36 mg/kg, twice daily) in inhibiting the growth of the ascitic tumour. Methylglyoxal-N-acetyl-L-cysteine was four times less toxic than methylglyoxalalone but was marginally less effective against the ascitic form of the tumour. Doses of these adducts equivalent to 144 mg/kg per day of methylglyoxal were more effective P less than 0.05) than the optimal regime of methylglyoxal in inhibiting the solid tumour (67.5% inhibition compared to 51%). Treatment of mice bearing the ascitic form of Sarcoma 180 with five daily doses (i.p.) of an HPE-cysteine adduct equivalent to a dose of HPE alone of 32-256 mg/kg per day significantly increased survival time by comparison with controls. The adduct was 2-3 times more effective, dose-for-dose, than HPE alone in inhibiting tumour growth. Purified buffered methylglyoxal has an LD50 on continuous infusion into the right lateral tail vein in mice of more than 3.0 mg/g per day (seven days at 2.8 ml/day). Local oedema followed by tail necrosis occurs at doses in excess of 0.25-0.5 mg/g per day in mice bearing the solid forms of the syngeneic tumours: squamous carcinoma D; lymphosarcoma 1 (WH/Ht mice); and spontaneous mammary D5056 (CBA/CA mice). A maximum tumour volume growth delay of 3.4 days at Day 17 (P less than 0.001) after transplantation was observed after infusion of 0.5 mg/g per day methylglyoxal on Days 11-17 in the CBA/CA D40 syngeneic mammary tumour. Tumour regrowth after termination of therapy eliminated the significant difference between control and methylglyoxal-treated tumours by Day 27. Methylglyoxal infusion (0...



This paper is referenced by
10.2147/IJN.S78284
Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect
Aparajita Pal (2015)
Methylglyoxal metabolism in Leishmania infantum
Lídia Barata (2010)
10.1081/DMR-120015695
GLUTATHIONE CONJUGATES AND THEIR SYNTHETIC DERIVATIVES AS INHIBITORS OF GLUTATHIONE-DEPENDENT ENZYMES INVOLVED IN CANCER AND DRUG RESISTANCE
Danny Burg (2002)
10.1177/030089168907500410
Lipid Peroxidation and Cancer: A Critical Reconsideration
Mario Umberto Dianzani (1989)
10.1016/j.tiv.2018.11.001
Methylglyoxal disturbs the expression of antioxidant, apoptotic and glycation responsive genes and triggers programmed cell death in human leukocytes.
Alessandro de Souza Prestes (2019)
Formation of cyclic adducts of deoxyguanosine with the aldehydes trans-4-hydroxy-2-hexenal and trans-4-hydroxy-2-nonenal in vitro.
C. K. Winter (1986)
10.1515/DMDI.2008.23.1-2.69
METHYLGLYOXAL AND GLUCOSE METABOLISM: A HISTORICAL PERSPECTIVE AND FUTURE AVENUES FOR RESEARCH
Miklós Péter Kalapos (2008)
10.1042/CS20050026
Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds.
Jorge Berlanga (2005)
10.1016/j.semcancer.2017.05.006
Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in cancer biology-Involvement in tumour suppression, tumour growth, multidrug resistance and target for chemotherapy.
Naila Rabbani (2018)
Protein glycation and methylglyoxal metabolism in Parkinson's disease
Hugo Vicente Miranda (2009)
10.1515/DMDI.2008.23.1-2.175
A BRIEF CRITICAL OVERVIEW OF THE BIOLOGICAL EFFECTS OF METHYLGLYOXAL AND FURTHER EVALUATION OF A METHYLGLYOXAL-BASED ANTICANCER FORMULATION IN TREATING CANCER PATIENTS
Dipa Talukdar (2008)
Characterisation of glyoxalase 1 mutant mouse and glyoxalase 1 copy number alteration
Alaa Shafie (2016)
10.1016/j.diabres.2019.01.002
Methylglyoxal, a potent inducer of AGEs, connects between diabetes and cancer.
Justine Bellier (2019)
10.1007/s10549-005-9078-7
A possible regulatory role of 17β-estradiol and tamoxifen on glyoxalase I and glyoxalase II genes expression in MCF7 and BT20 human breast cancer cells
Antonio Rulli (2005)
10.1038/s41598-017-12119-7
Hormetic potential of methylglyoxal, a side-product of glycolysis, in switching tumours from growth to death
Marie-Julie Nokin (2017)
10.1007/s10719-016-9705-z
Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics
Naila Rabbani (2016)
10.1042/BST20140011
Copy number variation of glyoxalase I.
Alaa Shafie (2014)
Semantic Scholar Logo Some data provided by SemanticScholar