Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells

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• 作者：Pei-Ching Hsiao (1) (2)
  Wei-Jiunn Lee (3)
  Shun-Fa Yang (4) (5)
  Peng Tan (6)
  Hui-Yu Chen (4)
  Liang-Ming Lee (3)
  Junn-Liang Chang (7) (8) (9)
  Gi-Ming Lai (10) (11)
  Jyh-Ming Chow (10)
  Ming-Hsien Chien (12) (6)
  
• 关键词：Nobiletin ; Apoptosis ; G0/G1 arrest ; Acute myeloid leukemia
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：35
• 期：12
• 页码：11903-11911
• 全文大小：953 KB
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• 作者单位：Pei-Ching Hsiao (1) (2)
  Wei-Jiunn Lee (3)
  Shun-Fa Yang (4) (5)
  Peng Tan (6)
  Hui-Yu Chen (4)
  Liang-Ming Lee (3)
  Junn-Liang Chang (7) (8) (9)
  Gi-Ming Lai (10) (11)
  Jyh-Ming Chow (10)
  Ming-Hsien Chien (12) (6)
  
  1. School of Medicine, Chung Shan Medical University, Taichung, Taiwan
  2. Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
  3. Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
  4. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
  5. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
  6. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
  7. Department of Medical Management, Taoyuan Armed Forces General Hospital, Taoyuan County, Taiwan
  8. School of Medicine, Pathology Department, National Defense Medical Center, Taipei, Taiwan
  9. Biomedical Engineering Department, Ming Chuan University, Taoyuan County, Taiwan
  10. Division of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 111 Hsing Long Road, Section 3, Taipei 116, Taiwan
  11. Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
  12. Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Nobiletin, a compound isolated from citrus fruits, is a polymethoxylated flavone derivative that was shown to have anti-inflammatory and anticancer activities in various solid tumors. The anticancer effect of nobiletin on nonsolid tumor remains unclear. Herein, the molecular mechanisms by which nobiletin exerts its anticancer effects on acute myeloid leukemia (AML) cells were investigated. The results showed that nobiletin suppressed cell proliferation in various types of AML cell lines. Moreover, nobiletin induced cell-cycle arrest of HL-60 AML cells at the G0/G1 phase by suppressing extracellular signal-regulated kinase (ERK) activity. Furthermore, nobiletin effectively induced apoptosis of HL-60 cells through caspase-8, caspase-9, and caspases-3 activation concomitantly with a marked induction of p38 mitogen-activated protein kinase (MAPK) activation, but without affecting expression levels of Bcl-2, Bax, or Bid. Taken together, our results suggest that nobiletin inhibited HL-60 cell proliferation through inducing cell-cycle arrest and apoptosis and could serve as a potential additional chemotherapeutic agent for treating AML.