Cargando…
Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol
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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635345/ https://www.ncbi.nlm.nih.gov/pubmed/19146708 http://dx.doi.org/10.1186/1742-4690-6-7 |
_version_ | 1782164172447940608 |
---|---|
author | Machijima, Yoshiaki Ishikawa, Chie Sawada, Shigeki Okudaira, Taeko Uchihara, Jun-nosuke Tanaka, Yuetsu Taira, Naoya Mori, Naoki |
author_facet | Machijima, Yoshiaki Ishikawa, Chie Sawada, Shigeki Okudaira, Taeko Uchihara, Jun-nosuke Tanaka, Yuetsu Taira, Naoya Mori, Naoki |
author_sort | Machijima, Yoshiaki |
collection | PubMed |
description | 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 G(1)/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. |
format | Text |
id | pubmed-2635345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26353452009-02-04 Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol Machijima, Yoshiaki Ishikawa, Chie Sawada, Shigeki Okudaira, Taeko Uchihara, Jun-nosuke Tanaka, Yuetsu Taira, Naoya Mori, Naoki Retrovirology Research 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 G(1)/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. BioMed Central 2009-01-16 /pmc/articles/PMC2635345/ /pubmed/19146708 http://dx.doi.org/10.1186/1742-4690-6-7 Text en Copyright © 2009 Machijima et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Machijima, Yoshiaki Ishikawa, Chie Sawada, Shigeki Okudaira, Taeko Uchihara, Jun-nosuke Tanaka, Yuetsu Taira, Naoya Mori, Naoki Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol |
title | Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol |
title_full | Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol |
title_fullStr | Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol |
title_full_unstemmed | Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol |
title_short | Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol |
title_sort | anti-adult t-cell leukemia/lymphoma effects of indole-3-carbinol |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635345/ https://www.ncbi.nlm.nih.gov/pubmed/19146708 http://dx.doi.org/10.1186/1742-4690-6-7 |
work_keys_str_mv | AT machijimayoshiaki antiadulttcellleukemialymphomaeffectsofindole3carbinol AT ishikawachie antiadulttcellleukemialymphomaeffectsofindole3carbinol AT sawadashigeki antiadulttcellleukemialymphomaeffectsofindole3carbinol AT okudairataeko antiadulttcellleukemialymphomaeffectsofindole3carbinol AT uchiharajunnosuke antiadulttcellleukemialymphomaeffectsofindole3carbinol AT tanakayuetsu antiadulttcellleukemialymphomaeffectsofindole3carbinol AT tairanaoya antiadulttcellleukemialymphomaeffectsofindole3carbinol AT morinaoki antiadulttcellleukemialymphomaeffectsofindole3carbinol |