Dataset Information

Effects of Lovastatin on MDA-MB-231 Breast Cancer Cells: An Antibody Microarray Analysis.

ABSTRACT: Despite the tremendous improvement in cancer therapeutics, treatment of late-stage breast cancer remains a challenge for both basic scientists and clinicians. Lovastatin, a natural product derived from Aspergillus terreus or Monascus ruber, has been widely used as cholesterol-lowing drug in the clinic. It also has anti-cancer properties through poorly defined molecular mechanisms. In the present study, we employed a novel antibody microarray technology to investigate the molecular mechanisms through which lovastatin inhibits breast cancer. We found that lovastatin up-regulated 17 proteins and down-regulated 20 proteins in MDA-MB-231 breast cancer cells. These included proteins that modulate apoptosis, cell proliferation, differentiation, signal transduction, epithelial-to-mesenchymal transition and tumor metastasis. Modulation of these pathways may mediate, in part, the inhibitory activity of lovastatin on breast cancer.

SUBMITTER: Yang T

PROVIDER: S-EPMC4716852 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Effects of Lovastatin on MDA-MB-231 Breast Cancer Cells: An Antibody Microarray Analysis.

Yang Tao T Yao Hui H He Guangchun G Song Liujiang L Liu Ning N Wang Yan Y Yang Yingke Y Keller Evan T ET Deng Xiyun X

Journal of Cancer 20160101 2

Despite the tremendous improvement in cancer therapeutics, treatment of late-stage breast cancer remains a challenge for both basic scientists and clinicians. Lovastatin, a natural product derived from Aspergillus terreus or Monascus ruber, has been widely used as cholesterol-lowing drug in the clinic. It also has anti-cancer properties through poorly defined molecular mechanisms. In the present study, we employed a novel antibody microarray technology to investigate the molecular mechanisms thr ...[more]

PMID: 26819643

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Project description:Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L) medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG) reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with 2-DG and metformin might provide an effective strategy to overcome metformin resistance of breast cancer cells.

Dataset Information

Effects of Lovastatin on MDA-MB-231 Breast Cancer Cells: An Antibody Microarray Analysis.

Publications

Effects of Lovastatin on MDA-MB-231 Breast Cancer Cells: An Antibody Microarray Analysis.

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