Open AccessTHIS ARTICLE HAS BEEN RETRACTED Anti‐adult T‐cell leukemia effects of a novel synthetic retinoid, Am80 (Tamibarotene)
Author(s) -
Nakazato Tetsuro,
Okudaira Taeko,
Ishikawa Chie,
Nakama Shinji,
Sawada Shigeki,
Tomita Mariko,
Uchihara Junnosuke,
Taira Naoya,
Masuda Masato,
Tanaka Yuetsu,
Ohshiro Kazuiku,
Takasu Nobuyuki,
Mori Naoki
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00917.x
Subject(s) - retinoid , apoptosis , retinoic acid , leukemia , cell growth , t cell leukemia , cell cycle , cell culture , cancer research , pharmacology , chemistry , biology , medicine , immunology , biochemistry , genetics
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)