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01.12.2014 | Research Article

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

verfasst von: 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

Erschienen in: Tumor Biology | Ausgabe 12/2014

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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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Titel: Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells
verfasst von: 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
Publikationsdatum: 01.12.2014
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 12/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-014-2457-0

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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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