Online citations, reference lists, and bibliographies.
← Back to Search

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

P. J. Conroy
Published 1978 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
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 references
Glyoxalase Activity of Liver from Rats Fed p-Dimethylaminoazobenzene
P. Cohen (1945)
10.1073/PNAS.54.1.200
Studies on autobiotics: chemical nature of retine.
L. G. Együd (1965)
10.1073/PNAS.56.1.203
On the regulation of cell division.
L. G. Együd (1966)
10.1259/0007-1285-39-457-19
The effect on cell survival of inhalation of oxygen under high pressure during irradiation in vivo of a solid mouse sarcoma.
H. Hewitt (1966)
Autoxidation of polyunsaturated esters in water: chemical structure and biological activity of the products.
E. Schauenstein (1967)
Nucleic acid and protein synthesis of malignant ascites cells in the presence of liver extract and methylglyoxal.
H. Otsuka (1967)
10.1016/0042-6822(67)90181-X
The effect of methylglyoxal on phage infection of Escherichia coli.
M. Baylor (1967)
10.1126/SCIENCE.161.3845.988
Bioelectronics. Intermolecular electron transfer may play a major role in biological regulation, defense, and cancer.
A. Szent-Györgyi (1968)
10.1126/SCIENCE.160.3832.1140
Cancerostatic action of methylglyoxal.
L. G. Együd (1968)
10.1016/0014-4827(68)90394-7
Inhibition of mammalian cell division by glyoxals.
C. T. Gregg (1968)
10.1016/s0021-9258(18)93430-7
Nonenzymic, polyvalent anion-catalyzed formation of methylglyoxal as an explanation of its presence in physiological systems.
V. Riddle (1968)
10.1021/BI00829A034
On the reaction of guanine with glyoxal, pyruvaldehyde, and kethoxal, and the structure of the acylguanines. A new synthesis of N2-alkylguanines.
R. Shapiro (1969)
10.1016/0006-291X(69)90445-8
Glyoxalase inhibitors as potential anticancer agents.
R. Vince (1969)
10.1021/BI00836A017
Structural studies on transfer ribonucleic acid. I. Labeling of exposed guanine sites in yeast phenylalanine transfer ribonucleic acid with kethoxal.
M. Litt (1969)
10.1007/BF00900595
Wirkungen von Hydroxypentenal auf den Stoffwechsel von Krebs-und Normalzellen
I. Bickis (1969)
Further studies on liver glyoxalase activity in mice bearing lymphosarcoma.
R. A. Strzinek (1970)
10.1007/BF00908565
Über den Mechanismus der durch 4-Hydroxypentenal bei Tumorzellen bewirkten Atmungshemmung
E. Schauenstein (1970)
10.1007/BF00909898
Kinetik der Reaktion von Sulfhydrylverbindungen mit α,β-ungesättigten Aldehyden in wäßrigem System
H. Esterbauer (1970)
10.1007/BF00284424
[Experiments on the therapeutical effect of 4-hydroxypentenal. 3. Inhibition of the growth of solid nemeth-kellner-lymphoma].
E. Schauenstein (1971)
10.1021/JM00283A009
Glyoxalase inhibitors. A possible approach to anticancer agents.
R. Vince (1971)
10.1021/JM00266A022
Glutaryl-S-(p-bromobenzyl)-L-cysteinylglycine. A metabolically stable inhibitor of glyoxalase I.
R. Vince (1973)
10.1016/0024-3205(74)90003-4
Electronic biology and its relation to cancer.
A. Szent-Györgyi (1974)
10.3181/00379727-148-38488
A Simple Method for Long-Term Drug Infusion in Mice: Evaluation of Guanazole as a Model 1
M. Paul (1975)
10.1515/znc-1975-7-808
Reaction of Glutathione with Conjugated Carbonyls
H. Esterbauer (1975)
10.1016/0014-2964(75)90003-1
Carcinostatic activity of 4-hydroxy-2-pent-en-1-al against transplantable murine tumour lines.
P. Conroy (1975)
10.1016/0014-2964(76)90065-7
Therapeutic effects of cysteine adducts of α,β-unsaturated aldehydes on Ehrlich ascites tumor of mice☆
H. Tillian (1976)
10.1016/0040-4020(76)87015-9
The reaction of cysteine with α,β-unsaturated aldehydes
H. Esterbauer (1976)
10.1016/0014-2964(77)90230-4
The inhibitory effects of a 4-hydroxypentenal: cysteine adduct against sarcoma 180 cells in mice.
P. Conroy (1977)



This paper is referenced by
10.3389/fonc.2021.645686
The Dual-Role of Methylglyoxal in Tumor Progression – Novel Therapeutic Approaches
A. Leone (2021)
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)
10.1016/j.diabres.2019.01.002
Methylglyoxal, a potent inducer of AGEs, connects between diabetes and cancer.
Justine Bellier (2019)
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.
N. Rabbani (2018)
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)
Characterisation of glyoxalase 1 mutant mouse and glyoxalase 1 copy number alteration
A. Shafie (2016)
10.1007/s10719-016-9705-z
Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics
N. Rabbani (2016)
10.2147/IJN.S78284
Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect
Aparajita Pal (2015)
10.1042/BST20140011
Copy number variation of glyoxalase I.
A. Shafie (2014)
Methylglyoxal metabolism in Leishmania infantum
Lídia Barata (2010)
Protein glycation and methylglyoxal metabolism in Parkinson's disease
H. V. 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
D. Talukdar (2008)
10.1515/DMDI.2008.23.1-2.69
METHYLGLYOXAL AND GLUCOSE METABOLISM: A HISTORICAL PERSPECTIVE AND FUTURE AVENUES FOR RESEARCH
M. P. Kalapos (2008)
10.1042/CS20050026
Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds.
J. Berlanga (2005)
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
A. Rulli (2005)
10.1081/DMR-120015695
GLUTATHIONE CONJUGATES AND THEIR SYNTHETIC DERIVATIVES AS INHIBITORS OF GLUTATHIONE-DEPENDENT ENZYMES INVOLVED IN CANCER AND DRUG RESISTANCE
D. Burg (2002)
10.1016/S0378-4274(99)00160-5
Methylglyoxal in living organisms: chemistry, biochemistry, toxicology and biological implications.
M. Kalapos (1999)
10.1016/0145-2126(95)00162-X
Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis.
Y. Kang (1996)
10.1016/1040-8428(94)00149-N
Advances in glyoxalase research. Glyoxalase expression in malignancy, anti-proliferative effects of methylglyoxal, glyoxalase I inhibitor diesters and S-D-lactoylglutathione, and methylglyoxal-modified protein binding and endocytosis by the advanced glycation endproduct receptor.
Paul J Thornalley (1995)
10.1016/0378-4274(94)90184-8
Methylglyoxal toxicity in mammals.
M. P. Kalapos (1994)
10.1016/0145-2126(93)90094-2
Inhibition of proliferation of human leukaemia 60 cells by methylglyoxal in vitro.
F. Ayoub (1993)
10.1016/0098-2997(93)90002-U
The glyoxalase system in health and disease.
Paul J Thornalley (1993)
10.1016/0006-2952(92)90680-H
Inhibition of proliferation of human leukaemia 60 cells by diethyl esters of glyoxalase inhibitors in vitro.
T. W. Lo (1992)
10.1002/CBF.290100104
Aldehyde‐induced modifications of the microtubular system in 3T3 fibroblasts
A. Olivero (1992)
10.1016/0887-2333(91)90038-F
Effects of methylglyoxal on adrenergic transmission in isolated rabbit intestine.
M. Rowan (1991)
10.1042/BJ2690001
The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life.
Paul J Thornalley (1990)
10.1016/0009-2797(89)90046-X
Effect of two aliphatic aldehydes, methylglyoxal and 4-hydroxypentenal, on the growth of Yoshida ascites hepatoma AH-130.
L. Tessitore (1989)
10.1177/030089168907500410
Lipid Peroxidation and Cancer: A Critical Reconsideration
M. Dianzani (1989)
10.1016/0166-6851(88)90059-X
D-lactate production by Leishmania braziliensis through the glyoxalase pathway.
T. Darling (1988)
10.1016/0009-2797(87)90023-8
Aliphatic aldehydes inhibit the proliferative response of human peripheral blood lymphocytes to phytohemagglutinin and alloantigens.
L. Tessitore (1987)
10.1007/978-3-642-71248-7_5
Effects of methylglyoxal on central and peripheral cholinergic responses.
M. Davies (1986)
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)
See more
Semantic Scholar Logo Some data provided by SemanticScholar