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Quercetin induces cell cycle arrest and apoptosis in CD133(+) cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin.

Atashpour S, Fouladdel S, Movahhed TK, Barzegar E, Ghahremani MH, Ostad SN, Azizi E - Iran J Basic Med Sci (2015)

Bottom Line: Quercetin has anticancer effects with the advantage of exhibiting low side effects.Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133(+) CSCs.The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran.

ABSTRACT

Objectives: The colorectal cancer stem cells (CSCs) with the CD133(+) 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 HT29 cancer cells and its isolated CD133(+) CSCs.

Materials and methods: The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction.

Results: The CD133(+) CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 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 G2/M arrest in the HT29 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 HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 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.

No MeSH data available.


Related in: MedlinePlus

Effects of quercetin on doxorubicin cytotoxicity in HT29 cancer cells. The HT29 cells were co-treated with different concentrations of Quer + Dox to determine cell proliferation using MTT assay. The results were expressed as mean±SE of three independent experiments in quadruplicate layout for each concentration. *denotes P<0.001 for significant difference between treatments in comparison to control RPMI. Dox: Doxorubicin; Quer: Quercetin
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Figure 3: Effects of quercetin on doxorubicin cytotoxicity in HT29 cancer cells. The HT29 cells were co-treated with different concentrations of Quer + Dox to determine cell proliferation using MTT assay. The results were expressed as mean±SE of three independent experiments in quadruplicate layout for each concentration. *denotes P<0.001 for significant difference between treatments in comparison to control RPMI. Dox: Doxorubicin; Quer: Quercetin

Mentions: The effect of quercetin (Quer) on cytotoxicity of Dox in HT29 cancer cells was determined using MTT assay. Co-treatment of HT29 cells with Quer and Dox resulted in significant sensitization of these cells to Dox chemotherapy (Figure 3). Quer at low concentration significantly reduced the IC50 of Dox from 750 nM to 250 nM in HT29 cancer cells. This demonstrates that Quer enhances the efficacy of Dox treatment and in turn reduces side effects of Dox, which are usually seen at higher concentrations of Dox in normal cells. comparison to parental HT29 cells. The IC50 of Dox and Quer alone that were determined on parental HT29 cancer cells showed 18% and 23% reduction in cell proliferation of CD133+ CSCs, respectively. Importantly, combination of Quer and Dox at low concentration was more effective in inhibiting the CSCs proliferation (28%) in comparison to Quer and Dox alone.


Quercetin induces cell cycle arrest and apoptosis in CD133(+) cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin.

Atashpour S, Fouladdel S, Movahhed TK, Barzegar E, Ghahremani MH, Ostad SN, Azizi E - Iran J Basic Med Sci (2015)

Effects of quercetin on doxorubicin cytotoxicity in HT29 cancer cells. The HT29 cells were co-treated with different concentrations of Quer + Dox to determine cell proliferation using MTT assay. The results were expressed as mean±SE of three independent experiments in quadruplicate layout for each concentration. *denotes P<0.001 for significant difference between treatments in comparison to control RPMI. Dox: Doxorubicin; Quer: Quercetin
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556754&req=5

Figure 3: Effects of quercetin on doxorubicin cytotoxicity in HT29 cancer cells. The HT29 cells were co-treated with different concentrations of Quer + Dox to determine cell proliferation using MTT assay. The results were expressed as mean±SE of three independent experiments in quadruplicate layout for each concentration. *denotes P<0.001 for significant difference between treatments in comparison to control RPMI. Dox: Doxorubicin; Quer: Quercetin
Mentions: The effect of quercetin (Quer) on cytotoxicity of Dox in HT29 cancer cells was determined using MTT assay. Co-treatment of HT29 cells with Quer and Dox resulted in significant sensitization of these cells to Dox chemotherapy (Figure 3). Quer at low concentration significantly reduced the IC50 of Dox from 750 nM to 250 nM in HT29 cancer cells. This demonstrates that Quer enhances the efficacy of Dox treatment and in turn reduces side effects of Dox, which are usually seen at higher concentrations of Dox in normal cells. comparison to parental HT29 cells. The IC50 of Dox and Quer alone that were determined on parental HT29 cancer cells showed 18% and 23% reduction in cell proliferation of CD133+ CSCs, respectively. Importantly, combination of Quer and Dox at low concentration was more effective in inhibiting the CSCs proliferation (28%) in comparison to Quer and Dox alone.

Bottom Line: Quercetin has anticancer effects with the advantage of exhibiting low side effects.Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133(+) CSCs.The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Molecular Research Lab, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran.

ABSTRACT

Objectives: The colorectal cancer stem cells (CSCs) with the CD133(+) 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 HT29 cancer cells and its isolated CD133(+) CSCs.

Materials and methods: The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction.

Results: The CD133(+) CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 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 G2/M arrest in the HT29 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 HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 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.

No MeSH data available.


Related in: MedlinePlus