title: Effects of methylglyoxal and glyoxalase I inhibition on breast cancer cells proliferation, invasion, and apoptosis through modulation of MAPKs, MMP9, and Bcl-2.
abstract: Emerging evidence indicates that methylglyoxal (MG) can inhibit tumorigenesis. Glyoxalase I (GLOI), a MG degradation enzyme, is implicated in the progression of human malignancies. However, little is known about the roles of MG and GLOI in breast cancer. Our purpose was to investigate the anticancer effects of MG and inhibition of GLOI on breast cancer cells and the underlying mechanisms of these effects. Our findings demonstrate that cell viability, migration, invasion, colony formation, and tubule formation were significantly restrained by addition of MG or inhibition of GLOI, while apoptosis was significantly increased. Furthermore, the expression of p-JNK, p-ERK, and p-p38 was markedly upregulated by addition of MG or inhibition of GLOI, whereas MMP-9 and Bcl-2 expression levels were dramatically decreased. These effects were augmented by combined treatment with MG and inhibition of GLOI. Collectively, these data indicate that MG or inhibition of GLOI induces anticancer effects in breast cancer cells and that these effects are potentiated by combination of the 2. These effects were modulated by activation of the MAPK family and downregulation of Bcl-2 and MMP-9. These findings may provide a new approach for the treatment of breast cancer.
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 , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
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 , China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Zhang
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 , China.
authors.forename: Xunjun
authors.initials: X
authors.lastname: Yang
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 , China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Lu
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 , China.
authors.forename: Xijuan
authors.initials: X
authors.lastname: Yan
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 , China.
authors.forename: Fanglan
authors.initials: F
authors.lastname: Xiao
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 , 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 , China.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Wen
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 , China.
authors.forename: Mengru
authors.initials: M
authors.lastname: Shi
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 , China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
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: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D063646:Carcinogenesis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D011765:Pyruvaldehyde / Q000008:administration & dosage*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D011765:Pyruvaldehyde; D020929:Mitogen-Activated Protein Kinase Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase
keywords: Bcl-2; MAPKs; MMP-9; Methylglyoxal; breast cancer cell line; glyoxalase I