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

Retrovirology. 2009 Jan 16;6:7. doi: 10.1186/1742-4690-6-7.

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 IkappaBalpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Cycle Proteins / drug effects
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • G1 Phase / drug effects
  • Human T-lymphotropic virus 1 / drug effects*
  • Human T-lymphotropic virus 1 / physiology
  • Humans
  • Indoles / administration & dosage
  • Indoles / pharmacology*
  • Indoles / therapeutic use*
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Mice
  • Mice, SCID
  • T-Lymphocytes* / drug effects
  • T-Lymphocytes* / virology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Indoles
  • indole-3-carbinol