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Title :Anti-adult T-cell leukemia effects of a novel synthetic retinoid, Am80 (Tamibarotene)
Authors :Nakazato, Tetsuro
Okudaira, Taeko
Ishikawa, Chie
Nakama, Shinji
Sawada, Shigeki
Tomita, Mariko
Uchihara, Jun-nosuke
Taira, Naoya
Masuda, Masato
Tanaka, Yuetsu
Ohshiro, Kazuiku
Takasu, Nobuyuki
Mori, Naoki
Issue Date :Nov-2008
Abstract :Clinical trials for treatment of adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) using all-trans-retinoic acid (ATRA) have shown satisfactory therapeutic responses, although efficacies were limited. Recently, many synthetic retinoids have been developed and among them, a novel synthetic retinoid, Am80 (Tamibarotene) is an RARα- and RARβ-specific retinoid expected to overcome ATRA resistance. The present study examined the inhibitory effects of Am80 on HTLV-I-infected T-cell lines and ATL cells. Am80 had negligible growth inhibition of peripheral blood mononuclear cells but marked growth inhibition of both HTLV-I-infected T-cell lines and ATL cells. Am80 arrested cells in the G1 phase of the cell cycle and induced apoptosis in HTLV-I-infected T-cell lines. It inhibited also the phosphorylation of IκBα and NF-κB-DNA binding, in conjunction with reduction of expression of proteins involved in the G1/S cell cycle transition and apoptosis. Am80 also inhibited the expression of JunD, resulting in suppression of AP-1-DNA binding. Furthermore, severe combined immunodeficient mice with tumors induced by subcutaneous inoculation of HTLV-I-infected T cells, responded to Am80 treatment with partial regression of tumors and no side-effects. These findings demonstrate that Am80 is a potential inhibitor of NF-κB and AP-1, and is a potentially useful therapeutic agent against ATL. (Cancer Sci 2008; 99: 2286–2294)
URL :http://www.blackwell-synergy.com/doi/abs/10.1111/j.1349-7006.2008.00917.x
Type Local :雑誌掲載論文
ISSN :1347-9032
Publisher :Blackwell Publishing
URI :http://hdl.handle.net/20.500.12000/12747
Citation :Cancer Science Vol.99 no.11 p.2286 -2294
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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