against CD44+/CD24- breast cancer stem cells. Elmira Barzegar a ... Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
Combination therapy of Berberine with Doxorubicin enhances anticancer properties against CD44+/CD24- breast cancer stem cells
a
a
a,b
a
Elmira Barzegar , Shamileh Fouladdel , Tahereh Komeili Movahhed , Shekoufeh Atashpour , Mohammad H. c
c
Ghahremani , Seyed Nasser Ostad , and Ebrahim Azizi
*a
a
Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences (TUMS), Tehran, Iran b c
Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran
Objectives: It is believed that cancer stem cells (CSCs) are responsible for therapeutic resistance, metastasis and tumor recurrence. Targeting breast cancer stem cells (BCSCs) is a potentially promising and effective strategy for breast cancer therapy. The scope of this study was to isolate BCSCs from MCF-7 breast cancer cell line and evaluate anticancer properties of Berberine (Brb) alone and in combination with Doxorubicin (Dox). Methods: The CD44+/CD24- CSCs from parental MCF-7 cell line were isolated using Magnetic-activated cell sorting (MACS) method with anti-CD44 and anti-CD24 conjugated microbeads. Isolated CD44+/CD24- CSCs and parental MCF-7 cells were treated with IC50 concentration of Brb and Dox alone and in combination. Inhibition of cell proliferation, cell cycle alterations and apoptosis induction were determined using MTT cytotoxicity assay and flow cytometry, respectively. Results: Unlike single compound treatment, co-treatment with Brb (25µM) and Dox (500 nM) for 48h significantly reduced the proliferation of CD44+/CD24- CSCs. Combination treatment also induced G0/G1 arrest and apoptosis in CD44+/CD24- CSCs.Conclusion: Results showed promising anticancer effects of combination of Brb and Dox against CD44+/CD24- CSCs in breast cancer cells that were resistant to Dox treatment alone. Further studies will enhance our understanding of mechanisms underlying targeted anticancer effects of Brb alone and in combination with Dox and possibly other chemotherapeutic drugs. Keywords: Breast cancer stem cells, Berberine, Doxorubicin, Cancer therapy
