Two α-dicarbonyls downregulate migration, invasion, and adhesion of liver cancer cells in a p53-dependent manner

Loarca, Lorena; Sassi-Gaha, Sihem; Artlett, Carol M.

doi:10.1016/j.dld.2013.05.005

Cited by 26 publications

(20 citation statements)

References 50 publications

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“…[12][13][14][25][26][27][28] The anti-tumor role of MG may also be attributed to its effects on cell migration. 15 Our results showing that MG inhibited the viability, proliferation, migration, and invasion of DLD-1 and SW480 colon cancer cells while promoting their apoptosis are in accordance with previous results in other cancer types. [12][13][14][25][26][27][28] There are multiple potential mechanisms by which MG may induce tumor suppression: (1) inhibition of the synthesis of proteins and nucleic acids via irreversible modification of protein, DNA, and RNA;…”

Section: Discussionsupporting

confidence: 80%

“…15 Moreover, AG abolished the MG-induced anti-tumor effects by acting as a scavenger, reacting rapidly with MG. 30 Cancer cells favor the aerobic glycolytic pathway and generate energy predominantly by increasing their rate of glycolysis. 24 MG is an intermediate metabolite of glucose.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] MG also inhibits tumor metastasis, enhances the immune response, and increases sensitivity to anti-tumor agents. [15][16][17][18] c-Myc is one of the most widely expressed human protooncogenes and is frequently overexpressed in colon cancer. 19 It has been shown to play an important role in the development and progression of this cancer.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…In addition, GLO1 reduces intracellular MGO levels. As a consequence, activation of p38 MAPK is decreased and the NFκB pathway is induced, which leads to inhibition of the proapoptotic Bax and p53 proteins, and enhanced expression of the antiapoptotic Bcl-2 protein [204,205]. Moreover, it was indicated that AP modification of HSP27 in human lung squamous cell carcinomas could play a role in the inhibition of caspase activation, and thereby prevent apoptosis [206].…”

Section: Cancermentioning

confidence: 99%

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

2015

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The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

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“…In addition, if methylglyoxal is not efficiently catalyzed by GLO1, the increased levels of methylglyoxal and AGEs induce the activation of p38/MAPK signaling, and reduce the activation of NF-κB signaling. This leads to the enhanced expression of the pro-apoptotic Bax and P53, and the decreased expression of the anti-apoptotic proteins, such as X-linked inhibitor of apoptosis protein (XIAP), survivin, Bcl-2 and Bcl-xL [31,32]. Therefore, GLO1 amplification and the increased expression and activity of GLO1 facilitate the detoxification of intracellular glyoxal and methylglyoxal to ensure tumor cell survival and proliferation.…”

Section: Regulatory Mechanisms Of Gloi In Tumor Cell Proliferation Anmentioning

confidence: 99%

Glyoxalase I in Tumor Cell Proliferation and Survival and as a Potential Target for Anticancer Therapy

Geng

Ma²,

Zhang³

et al. 2014

Oncol Res Treat

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SummaryGlyoxalase I (GLO1) belongs to the glyoxalase system, which catalyzes the conversion of deleterious methylglyoxal, mainly produced by glycolysis, to non-toxic D-lactate. The expression of GLO1 was up-regulated in tumor tissues with high metabolic rate, whereas inhibition of GLO1 expression led to the accumulation of glyoxal and methylglyoxal, significantly inducing cell damage or apoptosis. This suggests that GLO1 may play an important role in tumor cell proliferation and survival, and may represent a potential therapeutic target for tumors. Moreover, overexpression of GLO1 was associated with multidrug resistance in cancer chemotherapy. This review describes the role of GLO1 in tumor cell proliferation and survival, and the potential of GLO1 as a biomarker for tumor diagnosis and as a target for anticancer drug development.

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Two α-dicarbonyls downregulate migration, invasion, and adhesion of liver cancer cells in a p53-dependent manner

Cited by 26 publications

References 50 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

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

Glyoxalase I in Tumor Cell Proliferation and Survival and as a Potential Target for Anticancer Therapy

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