title: Effects of ADMA on gene expression and metabolism in serum-starved LoVo cells.
abstract: Serum starvation is a typical way for inducing tumor cell apoptosis and stress. Asymmetric dimethylarginine (ADMA) is an endogenous metabolite. Our previous study reveals the plasma ADMA level is elevated in colon cancer patients, which can attenuate serum starvation-induced apoptosis in LoVo cells. In current study, we evaluated the effects of ADMA on gene expression and metabolism in serum-starved LoVo cells with gene microarray and metabolomic approaches. Our results indicated that 96 h serum starvation induced comprehensive alterations at transcriptional level, and most of them were restored by ADMA. The main signaling pathways induced by serum starvation included cancers-related pathways, pathways in cell death, apoptosis, and cell cycle etc. Meanwhile, the metabolomic data showed serum-starved cells were clearly separated with control cells, but not with ADMA-treated cells in PCA model. The identified differential metabolites indicated serum starvation significantly suppressed TCA cycle, altered glucose and fatty acids metabolism, as well as nucleic acids metabolism. However, very few differential metabolites were identified between ADMA and serum-starved cells. In summary, our current results indicated serum starvation profoundly altered the gene expression and metabolism of LoVo cells, whereas ADMA could restore most of the changes at transcriptional level, but not at metabolic level.
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese MedicineShanghai 201203, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Zheng
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 MedicineShanghai 201203, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: He
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 MedicineShanghai 201203, China.|Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.|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.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese MedicineShanghai 201203, China.
authors.forename: Houkai
authors.initials: H
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D003470:Culture Media / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D009696:Nucleic Acids / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
chemical_list: D003470:Culture Media; D005227:Fatty Acids; D009696:Nucleic Acids; C018524:N,N-dimethylarginine; D001120:Arginine