Shekoufeh Atashpour - Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran
Shamileh Fouladdel - Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran
Tahereh Komeili Movahhed - Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
Elmira Barzegar - Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Hossein Ghahremani - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Seyed Nasser Ostad - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Ebrahim Azizi - Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran

Objective(s):The colorectal cancer stem cells (CSCs) with the CD۱۳۳+ phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT۲۹ cancer cells and its isolated CD۱۳۳+ CSCs. Materials and Methods: The CSCs from HT۲۹ cells were isolated using CD۱۳۳ antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT۲۹ cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: The CD۱۳۳+ CSCs comprised about ۱۰% of HT۲۹ cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT۲۹ cells and to a lesser extent in CSCs. Quercetin enhanced cytotoxicity and apoptosis induction of Dox at low concentration in both cell populations. Quercetin and Dox and their combination induced G۲/M arrest in the HT۲۹ cells and to a lesser extent in CSCs. Conclusion:The CSCs were a minor population with a significantly high level of drug resistance within the HT۲۹ cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT۲۹ cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells.

Apoptosis, Cancer stem cells, Cell cycle, Doxorubicin, Drug resistance, Quercetin