Warburg Effect Inversion: Adiposity shifts central primary metabolism in MCF-7 breast cancer cells

LIFE SCIENCES

卷:223

Article

Luis, Carla^1,2,3  Duarte, Fernanda^1,4  Faria, Isabel¹  Jarak, Ivana^5,6  Oliveira, Pedro F.^3,6,7  Alves, Marco G.⁶  Soares, Raquel^2,3  Fernandes, Ruben^1,3,8 

[1] Polytech Porto ESS P PORTO, Sch Hlth, Porto, Portugal

[2] Univ Porto, Fac Med, Dept Biomed, Biochem Unit, Porto, Portugal

[3] Univ Porto, I3S, Porto, Portugal

[4] Porto Univ CHUP, CoreLab, Hosp Ctr, Porto, Portugal

[5] Univ Coimbra, Fac Sci & Technol, Ctr Funct Ecol, Dept Life Sci, Coimbra, Portugal

[6] Univ Porto, Lab Cell Biol, Unit Multidisciplinary Res Biomed UMIB, Dept Microscopy,Inst Biomed Sci Abel Salazar ICBA, Porto, Portugal

[7] Univ Porto, Fac Med, Dept Genet, Porto, Portugal

[8] Univ Santiago de Compostela, Fac Med, Galiza, Spain

关键词: Type 2 diabetes;    Obesity;    Breast Cancer;    MCF-7;    Metabolism;    Warburg effect;   

DOI  :  10.1016/j.lfs.2019.03.016

来源: Elsevier

【 摘 要 】

Aims: Obesity is a complex health disorder and a trigger to many diseases like Diabetes mellitus (DM) and breast cancer (BrCa), both leading causes of morbidity and mortality worldwide. Also evidence demonstrates that abnormal glucose metabolism termed 'the Warburg effect' in cancer cell is closely associated with malignant phenotypes and promote the aggressiveness of several types of cancer, including BrCa. In this study, we evaluated the breast cancer cell metabolism in normoglycemia, hyperglycemia and in an obesity condition in order to clarify the potential underlined mechanisms that link these disorders. Materials and methods: MCF-7 cells were exposed to low and high glucose levels, the latter either in the presence of 3T3-L1 adipocyte conditioned medium (CM), thus mimicking the adiposity observed in obese patients. Cell viability, migration, proliferation, cytotoxicity and cell death assays were performed under the different culture conditions. Hormonal and lipid profile were also characterized by biochemical assays and primary metabolism was determined by Nuclear Magnetic Resonance (NMR)-based metabolomics. Results: Our results show an increased aggressiveness in the condition mimicking diabetogenic obesity with an altered energy/lipid metabolism. Interestingly in the experimental obesity-mimicking status, lipids and amino acids were expended while glucose was produced by tumor cells from lactate. These findings reveal a shift on tumor cells metabolism that is opposite to 'the Warburg effect'. Conclusions: Overall, this experimentally obesity-mimicking condition not only revealed an increased tumor proliferation and aggressiveness but also disclosed a new mechanism of cancer metabolism, the ` Warburg Effect Inversion'.

【 授权许可】

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