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Antiproliferative Effects of Metformin in Triple Negative MDA‐MB 231 Breast Cancer Cells Exposed to Glucose‐Starved And 2‐Deoxyglucose
Author(s) -
Triggle Christopher,
Majeed Yasser,
Samuel Samson Mathews,
Ding Hong Mathews
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb669
Subject(s) - metformin , propidium iodide , triple negative breast cancer , viability assay , autophagy , mtt assay , endocrinology , medicine , pi3k/akt/mtor pathway , chemistry , cancer research , breast cancer , cell growth , cancer , cell , insulin , apoptosis , programmed cell death , biochemistry
We have previously reported that 50μM of the anti‐diabetic drug metformin protects endothelial cells against hyperglycemia‐induced endothelial dysfunction and senescence thus providing support for the vascular protective benefits of metformin when used in diabetes 1,2. However, when 2mM (but not 50μM) metformin was used in a cell culture protocol with tumor murine microvascular endothelial in a glucose‐starved (GS) or 2‐deoxyglucose (2DG; 5mM) media pro‐survival autophagy and the mTOR pathway were inhibited and cell viability was reduced 3. These data supported other published evidence from both clinical and ex vivo cell‐based studies suggesting the utility of metformin for the treatment of various cancers. We therefore postulated that triple‐negative breast cancer (TNBC) that does not benefit from hormonal or HER2 targeted therapies may also respond to a metformin and GS/2DG protocol and investigated the effects of metformin in MDA‐MB 231 TNBC cells that were cultured in the presence of 2DG. Methods MDA‐MB 231 cells were treated with 2DG (10mM) in a glucose free media for 48h in the absence/presence of metformin (2mM). Western blot analysis (n=3–4); cell proliferation (MTT assay; n=5); migration (Radius Cell Migration Assay; n=4) and viability (propidium iodide assay; n=5) were performed. Significance was determined by ANOVA. Results Cell proliferation rate significantly decreased (95%) in 1) GS + metformin when compared to non‐treated GS (88%) and 2) 2DG exposed cells treated with metformin (46%) versus cells that were treated with either metformin (20%) or 2DG (28%) alone. Cell viability significantly (P<0.05) decreased in GS treated with metformin (34%) when compared to non‐treated GS (8%). In addition cell migration in cells exposed to 2DG and treated with metformin was reduced. Western blot analysis revealed that treatment with metformin significantly decreased (fold change) the levels of LC3A‐II (2.4&1.8) and LC3B‐II (2.3&1.6), pmTOR (S2448; 1.6&1.4) and downstream p4E‐BP1(T36/47; 1.5&1.3), pS6(S235/236; 4.7&2.8) and pS6(S240/244; 3.2&1.8) in GS and 2DG‐exposed cells + 2mM metformin. Conclusion Results show that using mM metformin in TNBC cells in a GS media containing 2DG offers a potential adjunct anti‐cancer protocol for the treatment of TNBC. Support or Funding Information Supported by a Qatar Foundation National Priorities Research Program grant (NPRP: 04‐910‐3‐244) and a Junior Scientist Research Experience Program grant (JSREP: 03‐016‐3‐009) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .