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Research ArticleExperimental Studies

Antiproliferative and Apoptosis-inducing Activity of Nobiletin Against Three Subtypes of Human Breast Cancer Cell Lines

CHEN CHEN, MISAKI ONO, MIKAKO TAKESHIMA and SHUJI NAKANO
Anticancer Research April 2014, 34 (4) 1785-1792;
CHEN CHEN
Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan
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MISAKI ONO
Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan
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MIKAKO TAKESHIMA
Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan
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SHUJI NAKANO
Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Fukuoka, Japan
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  • For correspondence: snakano@nakamura-u.ac.jp
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Abstract

Although nobiletin has a potent antitumor activity against several types of human cancers, its inhibitory effects and possible mechanisms of action on breast cancer cells with different hormone receptor and HER2 status remains unknown. Materials and Methods: Using hormone receptor-positive MCF-7, HER2-positive SK-BR-3, and triple-negative MDA-MB-468 cell lines, we investigated the antitumor mechanisms of nobiletin. Results: Nobiletin exhibited dose- and time-dependent antitumor activity against these different subtypes of cell lines, with the greatest inhibition observed against the MDA-MB-468 cell line. Nobiletin induced cell-cycle arrest at the G0/G1 phase by suppressing ERK1/2 activity, with concomitant cyclin-D1 suppression and p21 up-regulation. Nobiletin induced apoptotic cell death by reducing Bcl-xL expression, without affecting Bax levels, and inhibited the activity of AKT and downstream mTOR in MDA-MB-468 cells, but not in other cell lines. Conclusion: The predominant anticancer activity of nobiletin in MDA-MB-468 cells suggests a potential role of nobiletin for the prevention of triple-negative breast cancer.

  • Apoptosis
  • breast cancer
  • G0/G1 arrest
  • nobiletin
  • triple-negative
  • Received December 18, 2013.
  • Revision received January 6, 2014.
  • Accepted January 8, 2014.
  • Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 34 (4)
Anticancer Research
Vol. 34, Issue 4
April 2014
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Antiproliferative and Apoptosis-inducing Activity of Nobiletin Against Three Subtypes of Human Breast Cancer Cell Lines
CHEN CHEN, MISAKI ONO, MIKAKO TAKESHIMA, SHUJI NAKANO
Anticancer Research Apr 2014, 34 (4) 1785-1792;

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Antiproliferative and Apoptosis-inducing Activity of Nobiletin Against Three Subtypes of Human Breast Cancer Cell Lines
CHEN CHEN, MISAKI ONO, MIKAKO TAKESHIMA, SHUJI NAKANO
Anticancer Research Apr 2014, 34 (4) 1785-1792;
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Keywords

  • apoptosis
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  • nobiletin
  • Triple-negative
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