title: 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.
abstract: Methylglyoxal (MG) is a highly reactive dicarbonyl compound exhibiting anti-tumor activity. The anti-tumor 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.
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: He
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Huaibin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Xiaowan
authors.initials: X
authors.lastname: Chen
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Li
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Jiating
authors.initials: J
authors.lastname: Mao
authors.affiliation: a Key Laboratory of Laboratory Medicine , Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang , China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lyu
authors.affiliation: b Department of Laboratory Medicine , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Qing H
authors.initials: QH
authors.lastname: Meng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011765:Pyruvaldehyde / Q000494:pharmacology*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D011765:Pyruvaldehyde
keywords: Anti-tumor; c-Myc; colon cancer; glycolysis; methylglyoxal