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

Pei Ching Hsiao, Wei-Jiunn Lee, Shun Fa Yang, Peng Tan, Hui Yu Chen, Liang-Ming Lee, Junn Liang Chang, Gi-Ming Lai, Jyh-Ming Chow, Ming-Hsien Chien

研究成果: 雜誌貢獻文章

22 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)11903-11911
頁數9
期刊Tumor Biology
35
發行號12
DOIs
出版狀態已發佈 - 十二月 1 2014

指紋

Caspase 9
Caspase 8
Myeloid Cells
Acute Myeloid Leukemia
Apoptosis
flavone
HL-60 Cells
Cell Cycle Checkpoints
Cell Proliferation
Cell Cycle Resting Phase
Citrus
Extracellular Signal-Regulated MAP Kinases
G1 Phase
p38 Mitogen-Activated Protein Kinases
nobiletin
Caspase 3
Neoplasms
Anti-Inflammatory Agents
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

引用此文

Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells. / Hsiao, Pei Ching; Lee, Wei-Jiunn; Yang, Shun Fa; Tan, Peng; Chen, Hui Yu; Lee, Liang-Ming; Chang, Junn Liang; Lai, Gi-Ming; Chow, Jyh-Ming; Chien, Ming-Hsien.

於: Tumor Biology, 卷 35, 編號 12, 01.12.2014, p. 11903-11911.

研究成果: 雜誌貢獻文章

Hsiao, Pei Ching ; Lee, Wei-Jiunn ; Yang, Shun Fa ; Tan, Peng ; Chen, Hui Yu ; Lee, Liang-Ming ; Chang, Junn Liang ; Lai, Gi-Ming ; Chow, Jyh-Ming ; Chien, Ming-Hsien. / Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells. 於: Tumor Biology. 2014 ; 卷 35, 編號 12. 頁 11903-11911.
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abstract = "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.",
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AU - Lee, Wei-Jiunn

AU - Yang, Shun Fa

AU - Tan, Peng

AU - Chen, Hui Yu

AU - Lee, Liang-Ming

AU - Chang, Junn Liang

AU - Lai, Gi-Ming

AU - Chow, Jyh-Ming

AU - Chien, Ming-Hsien

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N2 - 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.

AB - 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.

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