SENSITIVITY OF BREAST CANCER STEM CELLS (CD24-/CD44+) TO DOXORUBICIN IS ASSOCIATED WITH OXIDATIVE STRESS STATUS

  • RESDA A. SYAHRANI Molecular Biology and Proteomics Core Facilities, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia
  • MELVA LOUISA Department of Pharmacology, Faculty of Medicine, Universitas Indonesia
  • SEPTELIA I. WANANDI Molecular Biology and Proteomics Core Facilities, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia

Abstract

Objective: The aim of this study was to analyze the sensitivity of BCSCs to doxorubicin and its association with oxidative stress.


Methods: BCSCs (CD24-/CD44+) were treated with doxorubicin every 2 d for 14 d. The determination of cell viability was performed using a trypan blue exclusion assay. The levels of reactive oxygen species (ROS) were measured using a dihydroethidium (DHE) and a 2’,7’-dichlorofluorescein diacetate (DCFH-DA) probes. Manganese superoxide dismutase (MnSOD) mRNA expression and specific activity were also analyzed. Glutathione (GSH) level was measured using Ellman’s method.


Results: The viability of the BCSCs decreased after 2 d of treatment with doxorubicin, but started to increase after 8 d. After 8 d of doxorubicin treatment, the ROS level in the BCSCs decreased, while the MnSOD specific activity increased. In addition, the MnSOD mRNA expression and GSH level were suppressed after 8 d of treatment.


Conclusion: Doxorubicin treatment induced cytotoxicity after 2 d by increasing the superoxide levels of the BCSCs. After 8 d of treatment, the sensitivity of BCSCs to doxorubicin decreased due to the suppressed oxidative stress from the enhanced antioxidant activity of the MnSOD.

Keywords: Breast cancer stem cells, Doxorubicin, GSH, MnSOD, Oxidative stress

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SYAHRANI, R. A., LOUISA, M., & WANANDI, S. I. (2019). SENSITIVITY OF BREAST CANCER STEM CELLS (CD24-/CD44+) TO DOXORUBICIN IS ASSOCIATED WITH OXIDATIVE STRESS STATUS. International Journal of Applied Pharmaceutics, 11(6), 91-96. https://doi.org/10.22159/ijap.2019.v11s6.33555
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