title: Curcumin Improves the Tumoricidal Effect of Mitomycin C by Suppressing ABCG2 Expression in Stem Cell-Like Breast Cancer Cells.
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.
authors: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Qianmei
authors: Q
authors: Zhou
authors: Longhua hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Meina
authors: M
authors: Ye
authors: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Yiyu
authors: Y
authors: Lu
authors: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Hui
authors: H
authors: Zhang
authors: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Qilong
authors: Q
authors: Chen
authors: Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA, United States of America.
authors: Shuang
authors: S
authors: Huang
authors: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Shibing
authors: S
authors: Su
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D061986:MCF-7 Cells; D016685:Mitomycin / Q000008:administration & dosage*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D007211:Indoles; D009363:Neoplasm Proteins; D016685:Mitomycin; D004317:Doxorubicin; C010522:tryptoquivaline; D003474:Curcumin