Inhibition of respiration of tumor cells by methylglyoxal and protection of inhibition by lactaldehyde

Ray, Manju; Halder, Jyotsnabaran; Dutta, Sriparna; Ray, Subhankar

doi:10.1002/ijc.2910470421

Cited by 41 publications

(28 citation statements)

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“…We have further observed that methylglyoxal specifically inhibits electron flow through complex I of the mitochondrial respiratory chain of EAC cells [4]. Interestingly, lactaldehyde, a catabolite of methylglyoxal, has been found to significantly protect both cellular [2] and mitochondrial [4] respiration in EAC cells. Methylglyoxal has also been found to inactivate glyceraldehyde-3-phosphate dehydrogenase (GA3PD, EC 1.2.1.12), a key enzyme of the glycolytic pathway, and this inactivation is responsible to a significant extent for the inhibition of glycolysis of EAC cells by methylglyoxal [3].…”

Section: Introductionmentioning

confidence: 62%

“…Recent work from our laboratory has clearly indicated that methylglyoxal is tumoricidal. 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].…”

Section: Introductionmentioning

confidence: 88%

“…Moreover, methylglyoxal has no inhibitory effect on NADH oxidation by submitochondrial particles of normal leucocytes. We have previously reported that -lactaldehyde, the product of enzymic reduction of methylglyoxal [15], could significantly protect the inhibitory effect of methylglyoxal on the viability [2] and mitochondrial respiration [4] of EAC cells. In the present study, by using leukaemic leucocyte mitochondria we have investigated the protective effect of lactaldehyde with various concentrations of lactaldehyde and methylglyoxal.…”

Section: Table 1 Effect Of Methylglyoxal On L-lactic Acid Formation Amentioning

confidence: 99%

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

Biswas

Ray

Misra

et al. 1997

Biochemical Journal

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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

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Section: Introductionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 88%

Section: Table 1 Effect Of Methylglyoxal On L-lactic Acid Formation Amentioning

confidence: 99%

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

Biswas

Ray

Misra

et al. 1997

Biochemical Journal

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“…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

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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.

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“…32 Briefly, cells were harvested for 8-10 days post-inoculation in female Swiss albino mice before being collected from the peritoneal cavity in 3 mL of normal saline (0.9% NaCl) and centrifuged (2,000× g) for 5 minutes at 4°C. The resulting pellets were washed again in normal saline before they were re-suspended in the requisite amount of PBS at pH 7.4.…”

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confidence: 99%

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

Pal

Talukdar

Roy

et al. 2015

IJN

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Purpose The normal metabolite methylglyoxal (MG) specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon normal cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest in developing a nanoparticulate drug delivery system to protect it and also to enhance its efficacy. Materials and methods MG-conjugated chitosan nanoparticles (Nano-MG) were prepared by conjugating the carbonyl group of MG with the amino group of chitosan polymer (Schiff’s base formation). Nano-MG were characterized in detail using the dynamic light scattering method, zeta potential measurement, Fourier transform infrared spectroscopy, and transmission electron microscopic analysis. Amount of MG anchored to Nano-MG, stability of Nano-MG, and in vitro release of MG from Nano-MG were estimated spectrophotometrically. Ehrlich ascites carcinoma (EAC) cells, human breast cancer cell line HBL-100, and lung epithelial adenocarcinoma cell line A549 were used as test systems to compare Nano-MG with bare MG in vitro. Cytotoxicity to EAC cells was evaluated by the trypan blue dye exclusion test, and cell viability of HBL-100 and A549 cells were studied using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of HBL-100 cells was assessed by flow cytometry and confocal microscopy. In vivo studies were performed on both EAC cells inoculated and also in sarcoma-180-induced solid tumor-bearing Swiss albino mice to assess the anticancer activity of Nano-MG in comparison to bare MG with varying doses, times, and administrative routes. Results Fourier transform infrared spectroscopy revealed the presence of imine groups in Nano-MG due to conjugation of the amino group of chitosan and carbonyl group of MG with diameters of nanoparticles ranging from 50–100 nm. The zeta potential of Nano-MG was +21 mV and they contained approximately 100 μg of MG in 1 mL of solution. In vitro studies with Nano-MG showed higher cytotoxicity and enhanced rate of apoptosis in the HBL-100 cell line in comparison with bare MG, but no detrimental effect on normal mouse myoblast cell line C2C12 at the concerned doses. Studies with EAC cells also showed increased cell death of nearly 1.5 times. Nano-MG had similar cytotoxic effects on A549 cells. In vivo studies further demonstrated the efficacy of Nano-MG over bare MG and found them to be about 400 times more potent in EAC-bearing mice and nearly 80 times more effective in sarcoma-180-bearing mice. Administration of ascorbic acid and creatine during in vivo treatments augmented the anticancer effect of Nano-MG. Conclusion The results clearly indicate that Nano-MG may constitute a promising tool in anticancer therapeutics in the near future.

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Inhibition of respiration of tumor cells by methylglyoxal and protection of inhibition by lactaldehyde

Cited by 41 publications

References 24 publications

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

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

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

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

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Inhibition of respiration of tumor cells by methylglyoxal and protection of inhibition by lactaldehyde

Cited by 41 publications

References 24 publications

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

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

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

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

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