1. Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines
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Tomita, Mariko, Kawakami, Hirochika, Uchihara, Jun-nosuke, Okudaira, Taeko, Masuda, Masato, Takasu, Nobuyuki, Matsuda, Takehiro, Ohta, Takao, Tanaka, Yuetsu, and Mori, Naoki
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HTLV-I infections , *T cells , *CELL lines , *ADULT T-cell leukemia - Abstract
Abstract: Activation of the activator protein 1 (AP-1) plays a critical role in oncogenesis by human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent of adult T-cell leukemia (ATL), and is required for maintenance of the malignant phenotype. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, has anti-tumor activity; however, the effect of curcumin against ATL has not been elucidated. In this study, we examined the effects of curcumin on AP-1 activity in HTLV-1-infected T-cell lines. Curcumin suppressed the constitutive AP-1 DNA-binding and transcriptional activity in HTLV-1-infected T-cell line. Curcumin also inhibited HTLV-1 Tax-induced AP-1 transcriptional activity. JunD was detectable as a major component of the AP-1–DNA complex in HTLV-1-infected T-cell lines using the supershift assay. The expression of JunD was suppressed by curcumin treatment. Curcumin inhibited the growth of HTLV-1-infected T-cell lines by inducing cell cycle arrest followed by apoptosis. Our results suggest that suppression of the constitutively active AP-1 by curcumin is due to, at least in-part, reducing the expression of JunD by curcumin. Inhibition of AP-1 activity by curcumin may be one of the mechanisms responsible for the anti-ATL effect of curcumin. We propose that curcumin is a potentially promising compound for the treatment of ATL. [Copyright &y& Elsevier]
- Published
- 2006
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