Inhibition of glycolysis and mitochondrial respiration of ehrlich ascites carcinoma cells by methylglyoxal

Halder, Jyotsnabaran; Ray, Manju; Ray, Subhankar

doi:10.1002/ijc.2910540315

Cited by 61 publications

(53 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, their inclusion of normal tissues and cells suggested that MG particularly inhibits the respiration of malignant cells but has no inhibitory effect on normal cells. [31][32][33] c-Myc has been reported to act as a pivotal regulator of cancer metabolism, directly regulating the glycolytic pathway. 34 Furthermore, MG also was demonstrated to activate the MAPK signaling pathway, which terminates in ERK-mediated c-Myc alteration.…”

Section: Discussionmentioning

confidence: 99%

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Zhou

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

Methylglyoxal (MG) is a highly reactive dicarbonyl compound exhibiting anti-tumor activity. The antitumor effects of MG have been demonstrated in some types of cancer, but its role in colon cancer and the mechanisms underlying this activity remain largely unknown. We investigated its role in human colon cancer and the underlying mechanism using human colon cancer cells and animal model. Viability, proliferation, and apoptosis were quantified in DLD-1 and SW480 colon cancer cells by using the Cell Counting Kit-8, plate colony formation assay, and flow cytometry, respectively. Cell migration and invasion were assessed by wound healing and transwell assays. Glucose consumption, lactate production, and intracellular ATP production also were assayed. The levels of c-Myc protein and mRNA were quantitated by western blot and qRT-PCR. The anti-tumor role of MG in vivo was investigated in a DLD-1 xenograft tumor model in nude mice. We demonstrated that MG inhibited viability, proliferation, migration, and invasion and induced apoptosis of DLD-1 and SW480 colon cancer cells. Treatment with MG reduced glucose consumption, lactate production, and ATP production and decreased c-Myc protein levels in these cells. Moreover, MG significantly suppressed tumor growth and c-Myc expression in vivo. Our findings suggest that MG plays an anti-tumor role in colon cancer. It inhibits cancer cell growth by altering the glycolytic pathway associated with downregulation of c-Myc protein. MG has therapeutic potential in colon cancer by interrupting cancer metabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Zhou

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…It specifically inhibits respiration in a wide variety of malignant cells, whereas the respiration in normal cells remains unaffected under identical conditions of incubation [2]. By using a model malignant cell, the Ehrlich ascites carcinoma (EAC) cell developed in mice, we have further shown that methylglyoxal inhibits both mitochondrial respiration and glycolysis in this type of cells [3]. As a consequence of inhibition of both mitochondrial respiration and glycolysis, ATP levels in these cells have been found to be critically reduced, rendering the cells non-viable [3].…”

Section: Introductionmentioning

confidence: 87%

“…By using a model malignant cell, the Ehrlich ascites carcinoma (EAC) cell developed in mice, we have further shown that methylglyoxal inhibits both mitochondrial respiration and glycolysis in this type of cells [3]. As a consequence of inhibition of both mitochondrial respiration and glycolysis, ATP levels in these cells have been found to be critically reduced, rendering the cells non-viable [3]. We have further observed that methylglyoxal specifically inhibits electron flow through complex I of the mitochondrial respiratory chain of EAC cells [4].…”

Section: Introductionmentioning

confidence: 99%

Selective inhibition of mitochondrial respiration and glycolysis in human leukaemic leucocytes by methylglyoxal

Biswas

Ray

Misra

et al. 1997

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

The effect of methylglyoxal on the oxygen consumption of mitochondria of both normal and leukaemic leucocytes was tested by using different respiratory substrates and complex specific artificial electron donors and inhibitors. The results indicate that methylglyoxal strongly inhibits mitochondrial respiration in leukaemic leucocytes, whereas, at a much higher concentration, methylglyoxal fails to inhibit mitochondrial respiration in normal leucocytes. Methylglyoxal strongly inhibits ADP-stimulated α-oxoglutarate and malate plus NAD + -dependent respiration, whereas, at a higher concentration, methylglyoxal fails to inhibit succinate and α-glycerophosphate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinone and cannot inhibit oxygen consumption when the N,N,Nh,Nh-tetramethyl-p-phenylenediamine by-pass is used. NADH oxidation by sub-mitochondrial particles of leukaemic leucocytes is also inhibited by

show abstract

“…After a period of 1-2 min the cell lysate was aspirated and boiled for 5 min. This was then diluted with a further 1 ml distilled water and 100 µl aliquots were mixed with a 100 µl aliquot of a luciferase/luciferin mixture provided by Sigma- Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was determined as described by Halder et al (1993). In brief, cells harvested from 75 cm 2 flasks were sonicated on ice in PBS to break cytosolic membranes.…”

Section: Cellular Atp Concentrations and Glyceraldehyde-3-phosphate Dmentioning

confidence: 99%

Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells

Newton¹,

bilko²,

Pappa³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

The oestrogen receptor is fundamental to the growth and survival of the rat pituitary tumour cell line, GH 3 . Our previous studies have shown that antioestrogens such as RU 58668 and ZM 182780 will reduce the rate of cell division and also induce cell death. Death of these cells in response to antioestrogen treatment appears to be due to a heightened sensitivity to reactive oxygen species (ROS). As part of a study to determine the cross-talk between steroid receptor systems in these cells, we have observed that the glucocorticoid, dexamethasone (Dex), inhibits antioestrogen-induced cell death. Cell death induced by H 2 O 2 is enhanced by ZM 182780 and this effect is also blocked by Dex. As apoptotic cell death in a number of systems involves an early loss of mitochondrial membrane potential ( m ), we have performed detailed studies on the time-course of m loss in relation to the loss in cell membrane function. These studies have indicated that a loss of m parallels a loss of cell membrane functionthis is more characteristic of necrosis than of apoptosis.From microscopic observations of these cells in response to H 2 O 2 , it has been noted that early cell membrane blebbing, induced by H 2 O 2 , is blocked in the presence of ZM 182780. Cell membrane blebbing can precede necrosis as well as apoptosis and it is thought to involve cytoskeletal changes, for which localised glycolytic reactions provide ATP. These observations, together with those showing that removal of glucose, but not inhibition of mitochondrial function, enhances ROS-induced cell death, prompted studies on the glycolytic pathway. As a strong candidate mechanism, it would appear that, via an effect on one of the rate-limiting glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase, Dex is able to overcome the antioestrogen-enhanced loss of glycolytic function following exposure of cells to ROS. This report contributes to the growing body of evidence showing that glucocorticoids provide a survival advantage to both normal and tumour cell types.

show abstract

Inhibition of glycolysis and mitochondrial respiration of ehrlich ascites carcinoma cells by methylglyoxal

Cited by 61 publications

References 18 publications

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Selective inhibition of mitochondrial respiration and glycolysis in human leukaemic leucocytes by methylglyoxal

Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells

Contact Info

Product

Resources

About