title: Curcumin-induced Aurora-A suppression not only causes mitotic defect and cell cycle arrest but also alters chemosensitivity to anticancer drugs.
abstract: Overexpression of oncoprotein Aurora-A increases drug resistance and promotes lung metastasis of breast cancer cells. Curcumin is an active anticancer compound in turmeric and curry. Here we observed that Aurora-A protein and kinase activity were reduced in curcumin-treated human breast chemoresistant nonmetastatic MCF-7 and highly metastatic cancer MDA-MB-231 cells. Curcumin acts in a similar manner to Aurora-A small interfering RNA (siRNA), resulting in monopolar spindle formation, S and G2/M arrest, and cell division reduction. Ectopic Aurora-A extinguished the curcumin effects. The anticancer effects of curcumin were enhanced by Aurora-A siRNA and produced additivity and synergism effects in cell division and monopolar phenotype, respectively. Combination treatment with curcumin overrode the chemoresistance to four Food and Drug Administration (FDA)-approved anticancer drugs (ixabepilone, cisplatin, vinorelbine, or everolimus) in MDA-MB-231 cells, which was characterized by a decrease in cell viability and the occurrence of an additivity or synergy effect. Ectopic expression of Aurora-A attenuated curcumin-enhanced chemosensitivity to these four tested drugs. A similar benefit of curcumin was observed in MCF-7 cells treated with ixabepilone, the primary systemic therapy to patients with invasive breast cancer (stages IIA-IIIB) before surgery. Antagonism effect was observed when MCF-7 cells were treated with curcumin plus cisplatin, vinorelbine or everolimus. Curcumin-induced enhancement in chemosensitivity was paralleled by significant increases (additivity or synergy effect) in apoptosis and cell cycle arrest at S and G2/M phases, the consequences of Aurora-A inhibition. These results suggest that a combination of curcumin with FDA-approved anticancer drugs warrants further assessment with a view to developing a novel clinical treatment for breast cancer.
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan.
authors.forename: Ching-Shiun
authors.initials: CS
authors.lastname: Ke
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Center of Infectious Disease and Signaling Research Center, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan.
authors.forename: Cheng-Hsin
authors.initials: CH
authors.lastname: Yen
authors.affiliation: Division of Hemato-oncology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung 802, Taiwan.
authors.forename: Guan-Cheng
authors.initials: GC
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Hung-Chi
authors.initials: HC
authors.lastname: Cheng
authors.affiliation: Institute of BioPharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan. Electronic address: chunlisu@ntnu.edu.tw.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Su
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D034741:RNA, Small Interfering
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; C576917:AURKA protein, human; D064096:Aurora Kinase A; D003474:Curcumin
keywords: Aurora-A; Chemosensitivity; Curcumin; FDA-approved anticancer drugs; Mitotic defects