Curcumin-induced Aurora-A suppression not only causes mitotic defect and cell cycle arrest but also alters chemosensitivity to anticancer drugs |
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| Institution: | 1. Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan;2. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;3. Center of Infectious Disease and Signaling Research Center, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;4. Division of Hemato-oncology, Department of Internal Medicine, Yuan''s General Hospital, Kaohsiung 802, Taiwan;5. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;6. Institute of BioPharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan;1. Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Taiwan;2. Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan;3. Institute of Basic Medicine Science, National Cheng Kung University, Tainan, Taiwan;4. Institute of Basic Medicine Science, Department of Cell Biology and Anatomy and Pathology, National Cheng Kung University, Tainan, Taiwan;5. Department of Medical Research China Medical University Hospital, Taichung, Taiwan;1. Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 411A, Oklahoma City, OK 73104, USA;2. Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, P. R. China;3. Departments of Pathology and Medicine, University of Colorado School of Medicine, Aurora, CO, USA |
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| 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. |
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