Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia.
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.
Rajasingh
Johnson
J
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
Raikwar
Himanshu P
HP
Muthian
Gladson
G
Johnson
Caroline
C
Bright
John J
JJ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D053616:Janus Kinase 3; D015458:Leukemia, T-Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D053634:TYK2 Kinase
D000972:Antineoplastic Agents, Phytogenic; D006131:Growth Inhibitors; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D053634:TYK2 Kinase; C070139:TYK2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin