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

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 10; pp. 4417 - 4424
• Main Authors: ITO, Keisuke, NAKAZATO, Tomonori, MING JI XIAN, YAMADA, Taketo, HOZUMI, Nobumichi, MURAKAMI, Akira, OHIGASHI, Hajime, IKEDA, Yasuo, KIZAKI, Masahiro
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.05.2005
• Subjects: Antineoplastic agents; Biological and medical sciences; Hematologic and hematopoietic diseases; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Pharmacology. Drug treatments; Tumors; Immunopathology; In vivo; Immunoglobulinopathy; Lymphoproliferative syndrome; Activity; Malignant hemopathy; Inhibitor; Acetate; Transcription factor NFκB; Myeloma; In vitro
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-0072

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.