Quercetin Effects on Cell Cycle Arrest and Apoptosis and Doxorubicin Activity in T47D Cancer Stem Cells

Abstract

Backgrounds: Targeting breast cancer stem cells with the CD44+/CD24-phenotype is critical for complete eradication of cancer cells due to its Self-renewal, differentiation, and therapeutic resistance ability. Quercetin is a popular flavonoid with lower adverse effects and has anti-tumor properties. Therefore, we assessed the anticancer activity of Quercetin and Doxorubicin alone and in combination in the T47D cells of human breast cancer and their isolated Cancer stem cells (CSCs). Materials and Methods: The human breast cancer cell line T47D was used for this experiment. T47D CSCs were isolated by magnetic bead sorting using the MACS system. The anticancer activity of Quercetin and Doxorubicin alone and in combination were evaluated using MTT cytotoxicity assay and cell cycle distribution and apoptosis induction by flow cytometry analysis. Results: We have shown that almost 1% of T47D cell populations are made up of CD44+/CD24-cells, which considered as cancer stem cells. Quercetin and Doxorubicin alone or in combination inhibited cell proliferation and induced apoptosis in breast cancer T47D cells and in lower extent in CD44+/CD24-cells. Quercetin significantly strengthened Doxorubicin's cytotoxicity and apoptosis induction in both cell populations. Quercetin and Doxorubicin and their combination induced G2/M arrest in the T47D cells and to a lesser extent in isolated CSCs. A value of p < 0.05 was considered as indicating a statistically significant difference. Conclusion: These outcomes suggested that CSCs are a minor population of cancer cells, which play a significant role in drug resistance by being quiescent, slow cycling and resistance to apoptosis. Furthermore, our data showed that adding Quercetin to Doxorubicin is an effective approach for the treatment of both CSCs and bulk tumor cells.

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“…QUE can also support conventional treatment methods. Studies performed using breast cancer cells showed that the addition of QUE to doxorubicin enhanced the induction of apoptosis in T47D cells [ 76 ]. In Figure 2 , the impact of flavonols on the regulation of apoptosis pathways is depicted.…”

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“…Dox, PTX, VCR, and QUE combined treatment substantially reduces ABCB1/P-gp expression and eliminates breast CSCs ( Li S. et al, 2018 ). Additionally, quercetin suppresses colorectal and breast CSCs ( Azizi et al, 2022 ). QUE can control HIF-1α, which re-sensitizes 4T1 cells, MCF-7/Dox cells, and HCT116 cancer cells to DDP and etoposide ( Kim et al, 2012 ).…”

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“…The antitumor aspect involves breast cancer, liver cancer, colon cancer, etc. [ 65 , 66 , 67 , 68 , 69 , 70 ]. However, there are application limitations related to the stability of use in vivo, which limits the use of quercetin [ 71 ].…”