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Curcumin Improves the Tumoricidal Effect of Mitomycin C by Suppressing ABCG2 Expression in Stem Cell-Like Breast Cancer Cells.

Zhou Q, Ye M, Lu Y, Zhang H, Chen Q, Huang S, Su S - PLoS ONE (2015)

Bottom Line: MMC or curcumin alone only marginally reduced the BCSC population in the mammospheres; however, together, they reduced the BCSC population in CD44+CD24-/low cells by more than 75% (29.34% to 6.86%).Curcumin sensitized BCSCs through a reduction in the expression of ATP-binding cassette (ABC) transporters ABCG2 and ABCC1.We demonstrated that fumitremorgin C, a selective ABCG2 inhibitor, reduced BCSC survival to a similar degree as curcumin did.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

ABSTRACT
Cancer cells with stem cell-like properties contribute to the development of resistance to chemotherapy and eventually to tumor relapses. The current study investigated the potential of curcumin to reduce breast cancer stem cell (BCSC) population for sensitizing breast cancer cells to mitomycin C (MMC) both in vitro and in vivo. Curcumin improved the sensitivity of paclitaxel, cisplatin, and doxorubicin in breast cancer cell lines MCF-7 and MDA-MB-231, as shown by the more than 2-fold decrease in the half-maximal inhibitory concentration of these chemotherapeutic agents. In addition, curcumin sensitized the BCSCs of MCF-7 and MDA-MB-231 to MMC by 5- and 15-fold, respectively. The BCSCs could not grow to the fifth generation in the presence of curcumin and MMC. MMC or curcumin alone only marginally reduced the BCSC population in the mammospheres; however, together, they reduced the BCSC population in CD44+CD24-/low cells by more than 75% (29.34% to 6.86%). Curcumin sensitized BCSCs through a reduction in the expression of ATP-binding cassette (ABC) transporters ABCG2 and ABCC1. We demonstrated that fumitremorgin C, a selective ABCG2 inhibitor, reduced BCSC survival to a similar degree as curcumin did. Curcumin sensitized breast cancer cells to chemotherapeutic drugs by reducing the BCSC population mainly through a reduction in the expression of ABCG2.

No MeSH data available.


Related in: MedlinePlus

Curcumin and MMC alone and together inhibited mammosphere formation in MCF-7 and MDA-MB-231 BCSCs.(A) MSFE of MCF-7 (a) and MDA-MB-231 (b) BCSCs treated with different doses of curcumin and MMC and their combination was calculated as the percentage of the number of mammosphere (diameter >50 μm) formed in 7 d/original number of cells seeded and is expressed as mean ± SD (n = 3). **P < 0.05, compared with MMC 0 μmol/L. *P < 0.05, compared with curcumin 5 μmol/L. #P < 0.05, compared with curcumin 20 μmol/L. (B) Self-renewal capacity of BCSCs was observed in curcumin 5 μmol/L and MMC 0.1 μmol/L alone and together in MCF-7 (a) and both curcumin 5 μmol/L and MMC 0.5 μmol/L alone or together in MDA-MB-231 (b). Data are presented as mean ± SD (n = 3). *P < 0.05, compared with control in different passages. (C) Curcumin sensitizes cancer stem cells and functions synergistically with MMC. Presented are representative flow cytometry dot plots for CD44 and CD24 cell marker expression in MDA-MB-231–derived BCSCs. a, untreated control; b, curcumin treatment; c, MMC treatment; and d, curcumin + MMC treatment.
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pone.0136694.g002: Curcumin and MMC alone and together inhibited mammosphere formation in MCF-7 and MDA-MB-231 BCSCs.(A) MSFE of MCF-7 (a) and MDA-MB-231 (b) BCSCs treated with different doses of curcumin and MMC and their combination was calculated as the percentage of the number of mammosphere (diameter >50 μm) formed in 7 d/original number of cells seeded and is expressed as mean ± SD (n = 3). **P < 0.05, compared with MMC 0 μmol/L. *P < 0.05, compared with curcumin 5 μmol/L. #P < 0.05, compared with curcumin 20 μmol/L. (B) Self-renewal capacity of BCSCs was observed in curcumin 5 μmol/L and MMC 0.1 μmol/L alone and together in MCF-7 (a) and both curcumin 5 μmol/L and MMC 0.5 μmol/L alone or together in MDA-MB-231 (b). Data are presented as mean ± SD (n = 3). *P < 0.05, compared with control in different passages. (C) Curcumin sensitizes cancer stem cells and functions synergistically with MMC. Presented are representative flow cytometry dot plots for CD44 and CD24 cell marker expression in MDA-MB-231–derived BCSCs. a, untreated control; b, curcumin treatment; c, MMC treatment; and d, curcumin + MMC treatment.

Mentions: To determine the effect of curcumin and MMC on the BCSC population, we treated MDA-MB-231- and MCF-7–derived BCSCs in the presence of curcumin only, MMC only, and both curcumin and MMC. The number of mammosphere structures formed revealed that curcumin at 5 μmol /L did not significantly alter the BCSC population in the 2 cell lines (Fig 2A). By contrast, MMC caused a dose-dependent reduction in the MSFE with an IC50 of 0.5 μmol/L for MCF-7 and 7.5 μmol/L for MDA-MB-231 cells (Fig 2A). Curcumin at 5 μmol/L and MMC at 0.1 μmol/L and 0.5 μmol/L reduced 50% of the MSFE in MCF-7 and MDA-MB-231 cells, respectively. Thus, a 5- and 15-fold reduction in the MMC concentration was required to achieve a 50% MSFE reduction in the 2 cell lines, respectively.


Curcumin Improves the Tumoricidal Effect of Mitomycin C by Suppressing ABCG2 Expression in Stem Cell-Like Breast Cancer Cells.

Zhou Q, Ye M, Lu Y, Zhang H, Chen Q, Huang S, Su S - PLoS ONE (2015)

Curcumin and MMC alone and together inhibited mammosphere formation in MCF-7 and MDA-MB-231 BCSCs.(A) MSFE of MCF-7 (a) and MDA-MB-231 (b) BCSCs treated with different doses of curcumin and MMC and their combination was calculated as the percentage of the number of mammosphere (diameter >50 μm) formed in 7 d/original number of cells seeded and is expressed as mean ± SD (n = 3). **P < 0.05, compared with MMC 0 μmol/L. *P < 0.05, compared with curcumin 5 μmol/L. #P < 0.05, compared with curcumin 20 μmol/L. (B) Self-renewal capacity of BCSCs was observed in curcumin 5 μmol/L and MMC 0.1 μmol/L alone and together in MCF-7 (a) and both curcumin 5 μmol/L and MMC 0.5 μmol/L alone or together in MDA-MB-231 (b). Data are presented as mean ± SD (n = 3). *P < 0.05, compared with control in different passages. (C) Curcumin sensitizes cancer stem cells and functions synergistically with MMC. Presented are representative flow cytometry dot plots for CD44 and CD24 cell marker expression in MDA-MB-231–derived BCSCs. a, untreated control; b, curcumin treatment; c, MMC treatment; and d, curcumin + MMC treatment.
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pone.0136694.g002: Curcumin and MMC alone and together inhibited mammosphere formation in MCF-7 and MDA-MB-231 BCSCs.(A) MSFE of MCF-7 (a) and MDA-MB-231 (b) BCSCs treated with different doses of curcumin and MMC and their combination was calculated as the percentage of the number of mammosphere (diameter >50 μm) formed in 7 d/original number of cells seeded and is expressed as mean ± SD (n = 3). **P < 0.05, compared with MMC 0 μmol/L. *P < 0.05, compared with curcumin 5 μmol/L. #P < 0.05, compared with curcumin 20 μmol/L. (B) Self-renewal capacity of BCSCs was observed in curcumin 5 μmol/L and MMC 0.1 μmol/L alone and together in MCF-7 (a) and both curcumin 5 μmol/L and MMC 0.5 μmol/L alone or together in MDA-MB-231 (b). Data are presented as mean ± SD (n = 3). *P < 0.05, compared with control in different passages. (C) Curcumin sensitizes cancer stem cells and functions synergistically with MMC. Presented are representative flow cytometry dot plots for CD44 and CD24 cell marker expression in MDA-MB-231–derived BCSCs. a, untreated control; b, curcumin treatment; c, MMC treatment; and d, curcumin + MMC treatment.
Mentions: To determine the effect of curcumin and MMC on the BCSC population, we treated MDA-MB-231- and MCF-7–derived BCSCs in the presence of curcumin only, MMC only, and both curcumin and MMC. The number of mammosphere structures formed revealed that curcumin at 5 μmol /L did not significantly alter the BCSC population in the 2 cell lines (Fig 2A). By contrast, MMC caused a dose-dependent reduction in the MSFE with an IC50 of 0.5 μmol/L for MCF-7 and 7.5 μmol/L for MDA-MB-231 cells (Fig 2A). Curcumin at 5 μmol/L and MMC at 0.1 μmol/L and 0.5 μmol/L reduced 50% of the MSFE in MCF-7 and MDA-MB-231 cells, respectively. Thus, a 5- and 15-fold reduction in the MMC concentration was required to achieve a 50% MSFE reduction in the 2 cell lines, respectively.

Bottom Line: MMC or curcumin alone only marginally reduced the BCSC population in the mammospheres; however, together, they reduced the BCSC population in CD44+CD24-/low cells by more than 75% (29.34% to 6.86%).Curcumin sensitized BCSCs through a reduction in the expression of ATP-binding cassette (ABC) transporters ABCG2 and ABCC1.We demonstrated that fumitremorgin C, a selective ABCG2 inhibitor, reduced BCSC survival to a similar degree as curcumin did.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

ABSTRACT
Cancer cells with stem cell-like properties contribute to the development of resistance to chemotherapy and eventually to tumor relapses. The current study investigated the potential of curcumin to reduce breast cancer stem cell (BCSC) population for sensitizing breast cancer cells to mitomycin C (MMC) both in vitro and in vivo. Curcumin improved the sensitivity of paclitaxel, cisplatin, and doxorubicin in breast cancer cell lines MCF-7 and MDA-MB-231, as shown by the more than 2-fold decrease in the half-maximal inhibitory concentration of these chemotherapeutic agents. In addition, curcumin sensitized the BCSCs of MCF-7 and MDA-MB-231 to MMC by 5- and 15-fold, respectively. The BCSCs could not grow to the fifth generation in the presence of curcumin and MMC. MMC or curcumin alone only marginally reduced the BCSC population in the mammospheres; however, together, they reduced the BCSC population in CD44+CD24-/low cells by more than 75% (29.34% to 6.86%). Curcumin sensitized BCSCs through a reduction in the expression of ATP-binding cassette (ABC) transporters ABCG2 and ABCC1. We demonstrated that fumitremorgin C, a selective ABCG2 inhibitor, reduced BCSC survival to a similar degree as curcumin did. Curcumin sensitized breast cancer cells to chemotherapeutic drugs by reducing the BCSC population mainly through a reduction in the expression of ABCG2.

No MeSH data available.


Related in: MedlinePlus