Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells.
Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by infection with human T-cell leukemia virus type I (HTLV-I) and remains incurable. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, can be potentially effective by promoting cell apoptosis. Here we examined whether curcumin is effective in the treatment of ATL. Curcumin prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells but not of normal peripheral blood mononuclear cells. Curcumin induced cell cycle arrest by reducing the expression of cyclin D1, Cdk1 and Cdc25C and apoptosis by reducing the expression of XIAP and survivin. Most of these genes are known to be regulated by NF-kappaB, which plays a critical role in oncogenesis by HTLV-I. Curcumin suppressed constitutive active NF-kappaB of HTLV-I-infected T-cell lines and primary ATL cells by inhibiting phosphorylation of IkappaBalpha. Curcumin also inhibited Tax-induced NF-kappaB transcriptional activity. However, curcumin-induced suppression of cell growth did not correlate with Tax expression level. Curcumin inhibited the growth of HTLV-I-infected T-cell tumors implanted subcutaneously in SCID mice. Our results indicate that curcumin has tumor-suppressive activity against ATL.
Tomita
Mariko
M
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Kawakami
Hirochika
H
Uchihara
Jun-nosuke
JN
Okudaira
Taeko
T
Masuda
Masato
M
Takasu
Nobuyuki
N
Matsuda
Takehiro
T
Ohta
Takao
T
Tanaka
Yuetsu
Y
Ohshiro
Kazuiku
K
Mori
Naoki
N
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000627:therapeutic use*; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D016356:Gene Products, tax / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015458:Leukemia, T-Cell / Q000188:drug therapy*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D000077022:Survivin; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D014407:Tumor Cells, Cultured; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D018797:Cell Cycle Proteins; D016356:Gene Products, tax; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D019938:Cyclin D1; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; C517010:Cdc25c protein, mouse; D020687:cdc25 Phosphatases; D003474:Curcumin