1′-acetoxychavicol acetate is a novel nuclear factor κB inhibitor with significant activity against multiple myeloma in vitro and in vivo

Keisuke Ito, Tomonori Nakazato, Ming Ji Xian, Taketo Yamada, Nobumichi Hozumi, Akira Murakami, Hajime Ohigashi, Yasuo Ikeda, Masahiro Kizaki

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

1′-Acetoxychavicol acetate (ACA) is a component of a traditional Asian condiment obtained from the rhizomes of the commonly used ethno-medicinal plant Languas galanga. Here, we show for the first time that ACA dramatically inhibits the cellular growth of human myeloma cells via the inhibition of nuclear factor κB (NF-κB) activity. In myeloma cells, cultivation with ACA induced G0-G1 phase cell cycle arrest, followed by apoptosis. Treatment with ACA induced caspase 3, 9, and 8 activities, suggesting that ACA-induced apoptosis in myeloma cells mediates both mitochondrial- and Fas-dependent pathways. Furthermore, we showed that ACA significantly inhibits the serine phosphorylation and degradation of IκBα. ACA rapidly decreased the nuclear expression of NF-κB, but increased the accumulation of cytosol NF-κB in RPMI8226 cells, indicating that ACA inhibits the translocation of NF-κB from the cytosol to the nucleus. To evaluate the effects of ACA in vivo, RPMI8226-transplanted NOD/SCID mice were treated with ACA. Tumor weight significantly decreased in the ACA-treated mice compared with the control mice. In conclusion, ACA has an inhibitory effect on NF-κB, and induces the apoptosis of myeloma cells in vitro and in vivo. ACA, therefore, provides a new biologically based therapy for the treatment of multiple myeloma patients as a novel NF-κB inhibitor.

Original languageEnglish
Pages (from-to)4417-4424
Number of pages8
JournalCancer Research
Volume65
Issue number10
DOIs
Publication statusPublished - 2005 May 15

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Multiple Myeloma
Apoptosis
1'-acetoxychavicol acetate
In Vitro Techniques
Cytosol
Condiments
Alpinia
G1 Phase Cell Cycle Checkpoints
Cell Cycle Resting Phase
Inbred NOD Mouse
Rhizome
SCID Mice
Caspase 9
Caspase 8
G1 Phase
Medicinal Plants
Tumor Burden
Caspase 3
Serine
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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1′-acetoxychavicol acetate is a novel nuclear factor κB inhibitor with significant activity against multiple myeloma in vitro and in vivo. / Ito, Keisuke; Nakazato, Tomonori; Xian, Ming Ji; Yamada, Taketo; Hozumi, Nobumichi; Murakami, Akira; Ohigashi, Hajime; Ikeda, Yasuo; Kizaki, Masahiro.

In: Cancer Research, Vol. 65, No. 10, 15.05.2005, p. 4417-4424.

Research output: Contribution to journalArticle

Ito, K, Nakazato, T, Xian, MJ, Yamada, T, Hozumi, N, Murakami, A, Ohigashi, H, Ikeda, Y & Kizaki, M 2005, '1′-acetoxychavicol acetate is a novel nuclear factor κB inhibitor with significant activity against multiple myeloma in vitro and in vivo', Cancer Research, vol. 65, no. 10, pp. 4417-4424. https://doi.org/10.1158/0008-5472.CAN-05-0072
Ito, Keisuke ; Nakazato, Tomonori ; Xian, Ming Ji ; Yamada, Taketo ; Hozumi, Nobumichi ; Murakami, Akira ; Ohigashi, Hajime ; Ikeda, Yasuo ; Kizaki, Masahiro. / 1′-acetoxychavicol acetate is a novel nuclear factor κB inhibitor with significant activity against multiple myeloma in vitro and in vivo. In: Cancer Research. 2005 ; Vol. 65, No. 10. pp. 4417-4424.
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