Simvastatin potentiates doxorubicin activity against MCF‑7 breast cancer cells

  • Authors:
    • Benjaporn Buranrat
    • Wanwisa Suwannaloet
    • Jarinyaporn Naowaboot
  • View Affiliations

  • Published online on: August 21, 2017     https://doi.org/10.3892/ol.2017.6783
  • Pages: 6243-6250
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Abstract

Simvastatin is a low density lipoprotein‑lowering drug that is widely used to prevent and treat cardiovascular disease by inhibiting the mevalonate pathway. Simvastatin also exhibits inhibitory effects on a number of types of cancer. In the present study, the effects of simvastatin on the activity of doxorubicin in the breast cancer MCF‑7 cell line, and the mechanisms by which this interaction occurs were investigated. The effect of simvastatin and doxorubicin treatment, alone and in combination, on the growth of MCF‑7 cells was evaluated by a sulforhodamine B and colony formation assay. To delineate the mechanisms of cell death, the following parameters were measured: Reactive oxygen species (ROS) production using the fluorescence probe dihydroethidium; caspase 3 activity by the fluorometry method; gene expression by quantitative polymerase chain reaction; and apoptotic‑ and proliferative‑related protein levels by western blotting. MCF‑7 cell proliferation was significantly suppressed by 24‑48 h treatment with simvastatin alone. Doses of 10‑50 µM simvastatin also enhanced the cytotoxicity of doxorubicin against MCF‑7 cells in a dose‑dependent manner, and decreased the colony‑forming ability of MCF‑7 cells. Simvastatin alone or in combination with doxorubicin significantly increased ROS levels. Combination treatment significantly decreased expression of the cell cycle regulatory protein Ras‑related C3 botulinum toxin substrate 1 and numerous downstream proteins including cyclin‑dependent kinase (Cdk) 2, Cdk4 and Cdk6. Additionally, simvastatin in combination with doxorubicin significantly induced expression of the cyclin‑dependent kinase inhibitor p21, increased cytochrome c and caspase 3 expression and reduced cyclin D1 expression. In conclusion, simvastatin acts synergistically with the anticancer drug doxorubicin against MCF‑7 cells, possibly through a downregulation of the cell cycle or induction of apoptosis. Although additional studies are required, simvastatin and doxorubicin combination may be a reasonable regimen for the treatment of breast cancer.
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November-2017
Volume 14 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Buranrat B, Suwannaloet W and Naowaboot J: Simvastatin potentiates doxorubicin activity against MCF‑7 breast cancer cells. Oncol Lett 14: 6243-6250, 2017
APA
Buranrat, B., Suwannaloet, W., & Naowaboot, J. (2017). Simvastatin potentiates doxorubicin activity against MCF‑7 breast cancer cells. Oncology Letters, 14, 6243-6250. https://doi.org/10.3892/ol.2017.6783
MLA
Buranrat, B., Suwannaloet, W., Naowaboot, J."Simvastatin potentiates doxorubicin activity against MCF‑7 breast cancer cells". Oncology Letters 14.5 (2017): 6243-6250.
Chicago
Buranrat, B., Suwannaloet, W., Naowaboot, J."Simvastatin potentiates doxorubicin activity against MCF‑7 breast cancer cells". Oncology Letters 14, no. 5 (2017): 6243-6250. https://doi.org/10.3892/ol.2017.6783