| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics, Molecular Targets, and Chemical Biology |
B Inhibitor with Significant Activity against Multiple Myeloma In vitro and In vivo
1 Division of Hematology, Department of Internal Medicine and 2 Pathology, Keio University School of Medicine, Tokyo, Japan; 3 Institute of Biological Science, Science University of Tokyo, Chiba, Japan; and 4 Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan
Requests for reprints: Masahiro Kizaki, Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Phone: 81-3-5363-3785; Fax: 81-3-3353-3515; E-mail: makizaki{at}sc.itc.keio.ac.jp.
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
B (NF-
B) 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 I
B
. ACA rapidly decreased the nuclear expression of NF-
B, but increased the accumulation of cytosol NF-
B in RPMI8226 cells, indicating that ACA inhibits the translocation of NF-
B 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-
B, 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-
B inhibitor.
This article has been cited by other articles:
![]() |
T. Hideshima, D. Chauhan, T. Kiziltepe, H. Ikeda, Y. Okawa, K. Podar, N. Raje, A. Protopopov, N. C. Munshi, P. G. Richardson, et al. Biologic sequelae of I{kappa}B kinase (IKK) inhibition in multiple myeloma: therapeutic implications Blood, May 21, 2009; 113(21): 5228 - 5236. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Hideshima, P. Neri, P. Tassone, H. Yasui, K. Ishitsuka, N. Raje, D. Chauhan, K. Podar, C. Mitsiades, L. Dang, et al. MLN120B, a Novel I{kappa}B Kinase {beta} Inhibitor, Blocks Multiple Myeloma Cell Growth In vitro and In vivo. Clin. Cancer Res., October 1, 2006; 12(19): 5887 - 5894. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Ichikawa, A. Murakami, and B. B. Aggarwal 1'-Acetoxychavicol Acetate Inhibits RANKL-Induced Osteoclastic Differentiation of RAW 264.7 Monocytic Cells by Suppressing Nuclear Factor-{kappa}B Activation Mol. Cancer Res., April 1, 2006; 4(4): 275 - 281. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |