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|Title ||:||Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol|
|Authors ||:||Machijima, Yoshiaki|
|Issue Date ||:||16-Jan-2009 |
|Abstract ||:||[Background] Adult T-cell leukemia/lymphoma (ATLL) is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1), and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C), a naturally occurring component of Brassica vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both in vitro and in vivo.|
[Results] In the in vitro study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G1/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose) polymerase cleavage. I3C also suppressed IkappaB-alpha phosphorylation and JunD expression, resulting in inactivation of NF-kappaB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally), but not the vehicle control.
[Conclusion] Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.
|Type Local ||:||雑誌掲載論文|
|Publisher ||:||BioMed Central Ltd.|
|Citation ||:||Retrovirology Vol.6 p.7 |
|Appears in Collections||:||Peer-reviewed Journal Articles (Faculty of Medicine)|
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