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Suboptimal folic acid exposure rewires oncogenic metabolism and proteomics signatures to mediate human breast cancer malignancy.
Huang, Angel; Huang, Su-Yu; Shah, Pramod; Ku, Wei-Chi; Huang, Kuang-Ta; Liu, Yi-Fang; Su, Chun-Li; Huang, Rwei-Fen S.
Affiliation
  • Huang A; Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Huang SY; Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Shah P; Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Ku WC; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Huang KT; Ph.D. Program in Nutrition and Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Liu YF; Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan.
  • Su CL; Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taiwan.
  • Huang RS; Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan; Ph.D. Program in Nutrition and Food Science, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 034825@mail.fju.edu.tw.
J Nutr Biochem ; 106: 109000, 2022 08.
Article in En | MEDLINE | ID: mdl-35460832
Whether treatment with folic acid (FA) affects human breast cancer positively or negatively remains unclear. We subjected human Michigan Cancer Foundation-7 cells, a human breast cancer cell line, to suboptimal FA at low levels (10 nM; LF) and high levels (50 µM; HF) and investigated the molecular mechanisms underlying their effects through metabolic flux and systematic proteomics analyses. The data indicated that LF induced and HF aggravated 2-fold higher mitochondrial toxicity in terms of suppressed oxidative respiration, increased fermented glycolysis, and enhanced anchorage-independent oncospheroid formation. Quantitative proteomics and Gene Ontology enrichment analysis were used to profile LF- and HF-altered proteins involved in metabolism, apoptosis, and malignancy pathways. Through STRING analysis, we identified a connection network between LF- and HF-altered proteins with mammalian target of rapamycin (mTOR). Rapamycin-induced blockage of mTOR complex 1 (mTORC1) signaling, which regulates metabolism, differentially inhibited LF- and HF-modulated protein signatures of mitochondrial NADH dehydrogenase ubiquinone flavoprotein 2, mitochondrial glutathione peroxidase 4, kynureninase, and alpha-crystallin B chain as well as programmed cell death 5 in transcript levels; it subsequently diminished apoptosis and oncospheroid formation in LF/HF-exposed cells. Taken together, our data indicate that suboptimal FA treatment rewired oncogenic metabolism and mTORC1-mediated proteomics signatures to promote breast cancer development.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Folic Acid Limits: Female / Humans Language: En Journal: J Nutr Biochem Journal subject: BIOQUIMICA / CIENCIAS DA NUTRICAO Year: 2022 Document type: Article Affiliation country: Taiwan Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Folic Acid Limits: Female / Humans Language: En Journal: J Nutr Biochem Journal subject: BIOQUIMICA / CIENCIAS DA NUTRICAO Year: 2022 Document type: Article Affiliation country: Taiwan Country of publication: United States