Curcumin-induced aurora-a suppression not only causes mitotic defect and cell cycle arrest but also alters chemosensitivity to anticancer drugs

Ching Shiun Ke, Hsiao-Sheng Liu, Cheng Hsin Yen, Guan Cheng Huang, Hung-Chi Cheng, Chi Ying F. Huang, Chun Li Su

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)526-539
Number of pages14
JournalJournal of Nutritional Biochemistry
Volume25
Issue number5
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Curcumin
Cell Cycle Checkpoints
Cells
Defects
Pharmaceutical Preparations
Cell Division
MCF-7 Cells
United States Food and Drug Administration
Breast Neoplasms
Small Interfering RNA
Cisplatin
Aurora Kinase A
Curcuma
G2 Phase
Oncogene Proteins
Drug Resistance
Protein Kinases
Surgery
Cell Survival
Breast

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

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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.",
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Curcumin-induced aurora-a suppression not only causes mitotic defect and cell cycle arrest but also alters chemosensitivity to anticancer drugs. / Ke, Ching Shiun; Liu, Hsiao-Sheng; Yen, Cheng Hsin; Huang, Guan Cheng; Cheng, Hung-Chi; Huang, Chi Ying F.; Su, Chun Li.

In: Journal of Nutritional Biochemistry, Vol. 25, No. 5, 01.01.2014, p. 526-539.

Research output: Contribution to journalArticle

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