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Title: Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia

Abstract

Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia.

Authors:
 [1];  [1];  [1];  [1];  [2]
  1. Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212 (United States)
  2. Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212 (United States) and Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37212 (United States). E-mail: jbright1@clarian.org
Publication Date:
OSTI Identifier:
20798790
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 340; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2005.12.014; PII: S0006-291X(05)02734-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL PROLIFERATION; CURCUMIN; GROWTH; IN VITRO; INFLAMMATION; INHIBITION; INJURIES; LEUKEMIA; PHOSPHORYLATION; PIGMENTS; PLANTS; PROTEINS

Citation Formats

Rajasingh, Johnson, Raikwar, Himanshu P., Muthian, Gladson, Johnson, Caroline, and Bright, John J.. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2005.12.014.
Rajasingh, Johnson, Raikwar, Himanshu P., Muthian, Gladson, Johnson, Caroline, & Bright, John J.. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia. United States. doi:10.1016/j.bbrc.2005.12.014.
Rajasingh, Johnson, Raikwar, Himanshu P., Muthian, Gladson, Johnson, Caroline, and Bright, John J.. Fri . "Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia". United States. doi:10.1016/j.bbrc.2005.12.014.
@article{osti_20798790,
title = {Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia},
author = {Rajasingh, Johnson and Raikwar, Himanshu P. and Muthian, Gladson and Johnson, Caroline and Bright, John J.},
abstractNote = {Adult T cell leukemia is an aggressive and frequently fatal malignancy that expressess constitutively activated growth-signaling pathways in association with deregulated growth and resistance to apoptosis. Curcumin (diferuloylmethane) is a naturally occurring yellow pigment, isolated from the rhizomes of the plant Curcuma longa that has traditionally been used in the treatment of injury and inflammation. But the effect and mechanism of action of curcumin on T cell leukemia is not known. To investigate the antitumor activity of curcumin in T cell leukemia, we examined its effect on constitutive phosphorylation of JAK and STAT proteins, proliferation, and apoptosis in HTLV-I-transformed T cell lines. HTLV-I-transformed T cell leukemia lines, MT-2, HuT-102, and SLB-1, express constitutively phosphorylated JAK3, TYK2, STAT3, and STAT5 signaling proteins. In vitro treatment with curcumin induced a dose-dependent decrease in JAK and STAT phosphorylation resulting in the induction of growth-arrest and apoptosis in T cell leukemia. The induction of growth-arrest and apoptosis in association with the blockade of constitutively active JAK-STAT pathway suggests this be a mechanism by which curcumin induces antitumor activity in T cell leukemia.},
doi = {10.1016/j.bbrc.2005.12.014},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 340,
place = {United States},
year = {Fri Feb 10 00:00:00 EST 2006},
month = {Fri Feb 10 00:00:00 EST 2006}
}