title: Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration.
abstract: Metformin is a widely used anti-diabetic drug with potential anti-tumor activity. However, little is known about its global metabolic and transcriptional impacts on tumor cells. In current study, we performed a metabolic profiling on human-derived colon cancer LoVo cells treated by 10 mM metformin for 8, 24 and 48 h. An obvious time-dependent metabolic alteration was observed from 8 to 48 h, prior to the reduction of cell viability. A total of 47, 45 and 66 differential metabolites were identified between control and metformin-treated cells at three time points. Most of the metabolites were up-regulated at 8 h, but down-regulated at 24 and 48 h by metformin. These metabolites were mainly involved in carbohydrates, lipids, amino acids, vitamins and nucleotides metabolism pathways. Meanwhile, the transcirptomic profile revealed 134 and 3061 differentially expressed genes at 8 and 24 h by metformin. In addition to the cancer signaling pathways, expression of genes involved in cell energy metabolism pathways was significantly altered, which were further validated with genes in glucose metabolism pathway. Altogether, our current data indicate that metformin suppressed the proliferation of LoVo cells, which may be due to the modulation on cell energy metabolism at both metabolic and transcriptional levels in a time-dependent way.
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: He
authors.affiliation: Laboratory of Integrative Medicine Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Stable Isotope and Metabolomics Core Facility, Diabetes Center Albert Einstein College of Medicine, 1300 Morris Part Ave, Bronx, New York, 10461, USA.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, 96813, USA.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, 96813, USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.|Center for Translational Medicine, and Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.|Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, 96813, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.|School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Houkai
authors.initials: H
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008687:Metformin / Q000494:pharmacology*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin