Research

Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol

Yoshiaki Machijima¹ , Chie Ishikawa^1,2,3 , Shigeki Sawada^1,4 , Taeko Okudaira⁵ , Jun-nosuke Uchihara⁶ , Yuetsu Tanaka⁷ , Naoya Taira⁸ and Naoki Mori¹

¹  Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan

²  Division of Child Health and Welfare, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan

³  The Japanese Society for the Promotion of Science (JSPS), Japan

⁴  Division of Oral and Maxillofacial Functional Rehabilitation, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan

⁵  Division of Endocrinology and Metabolism, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan

⁶  Depertment of Internal Medicine, Naha City Hospital, 2-31-1 Furujima, Naha, Okinawa, Japan

⁷  Division of Immunology, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan

⁸  Department of Internal Medicine, Heartlife Hospital, 208 Iju, Nakagusuku, Okinawa, Japan

author email corresponding author email

Retrovirology 2009, 6:7doi:10.1186/1742-4690-6-7

Published:	16 January 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 IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB 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.