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  2. Bay 11-7082 inhibits transcription factor NF-kappaB and induces apoptosis of HTLV-I-infected T-cell lines and primary adult T-cell leukemia cells

Bay 11-7082 inhibits transcription factor NF-kappaB and induces apoptosis of HTLV-I-infected T-cell lines and primary adult T-cell leukemia cells

  • Blood. 2002 Sep 1;100(5):1828-34. doi: 10.1182/blood-2002-01-0151.
Naoki Mori 1 Yasuaki Yamada Shuichi Ikeda Yoshihiro Yamasaki Kunihiro Tsukasaki Yuetsu Tanaka Masao Tomonaga Naoki Yamamoto Masahiro Fujii
Affiliations

Affiliation

  • 1 Department of Preventive Medicine and AIDS Research, Institute of Tropical Medicine, Nagasaki University, Japan. n-mori@med.u-ryukyu.ac.jp
Abstract

Human T-cell leukemia virus type I (HTLV-I) is the causative agent of an aggressive form of leukemia designated adult T-cell leukemia (ATL). We have previously demonstrated that all T-cell lines infected with HTLV-I and primary leukemic cells from ATL patients display constitutively high activity of transcription factor NF-kappaB. In this study we showed that Bay 11-7082, an inhibitor of NF-kappaB, induced Apoptosis of HTLV-I-infected T-cell lines but only negligible Apoptosis of HTLV-I-negative T cells. Bay 11-7082 rapidly and efficiently reduced the DNA binding of NF-kappaB in HTLV-I-infected T-cell lines and down-regulated the expression of the antiapoptotic gene, Bcl-x(L), regulated by NF-kappaB, whereas it had little effect on the DNA binding of another transcription factor, AP-1. Although the viral protein Tax is an activator of NF-kappaB, Bay 11-7082-induced Apoptosis of HTLV-I-infected cells was not associated with reduced expression of Tax. Furthermore, Bay 11-7082- induced Apoptosis of primary ATL cells was more prominent than that of normal peripheral blood mononuclear cells, and Apoptosis of these cells was also associated with down-regulation of NF-kappaB activity. Our results indicate that NF-kappaB plays a crucial role in the pathogenesis and survival of HTLV-I-infected leukemic cells and that it is a suitable target for the prevention and treatment of ATL.

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