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

He, Tiantian; Zhou, Huaibin; Li, Chunmei; Chen, Yuan; Chen, Xiaowan; Li, Chenli; Mao, Jiating; Lyu, Jianxin; Meng, Qing H.

doi:10.1080/15384047.2016.1210736

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…Cell apoptosis was detected using the Annexin V-APC Apoptosis Detection kit (KeyGEN Biotech, Nanjing, China) as described in our previous studies and others [41,42,43,44]. Allophycocyanin (APC) is an accessory photosynthetic pigment found in blue-green algae.…”

Section: Methodsmentioning

confidence: 99%

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

Chen

Fang

Zhang

et al. 2017

IJMS

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GlyoxalaseI (GLOI) is an enzyme that catalyzes methylglyoxal metabolism. Overexpression of GLOI has been documented in numerous tumor tissues, including colorectal cancer (CRC). The antitumor effects of GLOI depletion have been demonstrated in some types of cancer, but its role in CRC and the mechanisms underlying this activity remain largely unknown. Our purpose was to investigate the antitumor effects of depleted GLOI on CRC in vitro and in vivo. RNA interference was used to deplete GLOI activity in four CRC cell lines. The cells’ proliferation, apoptosis, migration, and invasion were assessed by using the Cell Counting Kit-8, plate colony formation assay, flow cytometry, and transwell assays. Protein and mRNA levels were analyzed by western blot and quantitative real-time PCR (qRT-PCR), respectively. The antitumor effect of GLOI depletion in vivo was investigated in a SW620 xenograft tumor model in BALB/c nude mice. Our results show that GLOI is over-expressed in the CRC cell lines. GLOI depletion inhibited the proliferation, colony formation, migration, and invasion and induced apoptosis of all CRC cells compared with the controls. The levels of signal transducer and activator of transcription 1 (STAT1), p53, and Bcl-2 assaciated X protein (Bax) were upregulated by GLOI depletion, while cellular homologue of avian myelocytomatosis virus oncogene (c-Myc) and B cell lymphoma/lewkmia-2 (Bcl-2) were downregulated. Moreover, the growth of SW620-induced CRC tumors in BALB/c nude mice was significantly attenuated by GLOI depletion. The expression levels of STAT1, p53, and Bax were increased and those of c-Myc and Bcl-2 were decreased in the GLOI-depleted tumors. Our findings demonstrate that GLOI depletion has an antitumor effect through the STAT1 or p53 signaling pathways in CRC, suggesting that GLOI is a potential therapeutic target.

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Section: Methodsmentioning

confidence: 99%

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

Chen

Fang

Zhang

et al. 2017

IJMS

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“…Recent studies demonstrated that ATB acts as a competing RNA by binding with microRNA (miR)-494 in lung cancer cells (28), miR-141-3p in gastric cancer cells (29), miR-590-5p in melanoma (30), and miR-200 family members in diverse types of cancer (18,26,31,32). ATB regulates transcriptional coactivator YAP1 (YAP1), NF-κB, p38 mitogen-activated protein kinase (MAPK), Twist, and TGF-β in lung cancer, glioma, breast cancer and malignant melanoma (23,30,33,34).…”

Section: Discussionmentioning

confidence: 99%

lncRNA‑ATB promotes stemness maintenance in colorectal cancer by regulating transcriptional activity of the β‑catenin pathway

et al. 2020

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Long non-coding RNA activated by transforming growth factor-β (ATB) was recently reported to be involved in a wide range of physiological and pathological processes. However, the role of ATB in colorectal cancer (CRC) stemness remains unclear. In the present study, the functional role of ATB in maintaining stemness of CRC was determined using colony formation and sphere formation assays, and xenograft models. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were performed to investigate the mechanisms underlying the effects of ATB. Knockdown of ATB impaired colony formation and sphere formation in CRC cells, accompanied by an inhibition of colon tumor growth. Further results suggested that ATB regulated the transcriptional activity of the β-catenin pathway by inhibiting β-catenin expression. In addition, the results confirmed the role of β-catenin in ATB-mediated regulation of stemness in CRC. Collectively, the results indicated that ATB is a promising therapeutic target for CRC.

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“…The cells were seeded into the upper chambers of the transwell culture plates (SW480, 8×10 4 cells; SW620, 1.2×10 5 cells; DLD-1, 8×10 4 cells; and HCT-15, 8×10 4 cells), and RPMI-1640 medium containing 20% FBS was placed in the lower chambers as a chemoattractant. The cells were seeded into the upper chambers of the transwell culture plates as described in our previous paper [ 13 ]. The invasion assay was similar to the migration assay except that the inserts were coated with 45 uL matrigel solution (matrigel: serum-free medium ratio 1:10).…”

Section: Methodsmentioning

confidence: 99%

“…Methylglyoxal (MG), an extremely reactive glucose metabolite, is an endogenous byproduct of glycolysis. It is mainly generated in the dephosphorylation of glycolytic intermediates and in metabolism of the polyol pathway and amino acetone [ 8 – 13 ]. MG was historically investigated as an antitumor agent, but sound scientific evidence of its efficacy is lacking [ 9 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…MG was historically investigated as an antitumor agent, but sound scientific evidence of its efficacy is lacking [ 9 – 16 ]. Previous studies from our laboratory showed that MG suppressed human colon cancer cell lines and tumor growth in a mouse model and had inhibitory effects against breast cancer [ 12 , 13 ]. MG has been reported to prevent tumor growth by inhibiting mitochondrial respiration in malignant cells [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Synergistic inhibition of colon cancer growth by the combination of methylglyoxal and silencing of glyoxalase I mediated by the STAT1 pathway

Yuan

Fang

et al. 2017

Oncotarget

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Methylglyoxal (MG), an extremely reactive glucose metabolite, exhibits antitumor activity. Glyoxalase I (GLOI), which catalyzes MG metabolism, is associated with the progression of human malignancies. While the roles of MG or GLOI have been demonstrated in some types of cancer, their effects in colon cancer and the mechanisms underlying these effects remain largely unknown. For this study, MG and GLOI levels were manipulated in colon cancer cells and the effects on their viability, proliferation, apoptosis, migration, and invasion in vitro were quantified by Cell Counting Kit-8, colony formation assay, flow cytometry, and transwell assays. The expression levels of STAT1 pathway–associated proteins and mRNAs in these cells were quantified by western blot and qRT-PCR, respectively. The antitumor effects of MG and silencing of GLOI were investigated in vivo in a SW620 colon cancer xenograft model in BALB/c nude mice. Our findings demonstrate that MG in combination with silencing of GLOI synergistically inhibited the cancer cells’ proliferation, colony formation, migration, and invasion and induced apoptosis in vitro compared with the controls. Furthermore, these treatments up-regulated STAT1 and Bax while down-regulating Bcl-2 in vitro. MG treatment alone or in combination with silencing of GLOI also reduced the growth of the SW620 tumors in mice by up-regulation of STAT1 and Bax and down-regulation of Bcl-2. Taken together, our findings suggest that MG in combination with silencing of GLOI merits further evaluation as a targeted therapeutic strategy for colon cancer.

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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

Cited by 18 publications

References 38 publications

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

Blockage of Glyoxalase I Inhibits Colorectal Tumorigenesis and Tumor Growth via Upregulation of STAT1, p53, and Bax and Downregulation of c-Myc and Bcl-2

lncRNA‑ATB promotes stemness maintenance in colorectal cancer by regulating transcriptional activity of the β‑catenin pathway

Synergistic inhibition of colon cancer growth by the combination of methylglyoxal and silencing of glyoxalase I mediated by the STAT1 pathway

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