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Title :Bisphosphonate incadronate inhibits growth of human T-cell leukaemia virus type I-infected T-cell lines and primary adult T-cell leukaemia cells by interfering with the mevalonate pathway
Authors :Ishikawa, Chie
Matsuda, Takehiro
Okudaira, Taeko
Tomita, Mariko
Kawakami, Hirochika
Tanaka, Yuetsu
Masuda, Masato
Ohshiro, Kazuiku
Ohta, Takao
Mori, Naoki
Issue Date :Feb-2007
Abstract :Anti-resorptive bisphosphonates are used for the treatment of hypercalcemia and bone complications associated with malignancies and osteoporosis, but have also been shown to have anti-tumour effects in various cancers. Adult T-cell leukaemia (ATL) is a fatal T-cell malignancy caused by infection with human T-cell leukaemia virus type I (HTLV-I), and remains incurable. ATL is associated with osteolytic bone lesions and hypercalcemia, which are major factors in the morbidity of ATL. Thus, the search for anti-ATL agents that have both anti-tumour and anti-resorptive activity is warranted. The bisphosphonate agent, incadronate prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells, but not of non-infected T-cell lines or normal peripheral blood mononuclear cells. Incadronate induced S-phase cell cycle arrest and apoptosis in HTLV-I-infected T-cell lines, and treatment of these cells with substrates of the mevalonate pathway blocked the incadronate-mediated growth suppression. Incadronate also prevented the prenylation of Rap1A protein. These results demonstrated that incadronate-induced growth suppression occurs by interfering with the mevalonate pathway. Importantly, treatment with incadronate reduced tumour formation from an HTLV-I-infected T-cell line, when these cells were inoculated subcutaneously into severe combined immunodeficient mice. These findings suggest that incadronate could be potentially useful for the treatment of ATL.
URL :http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2141.2006.06445.x
Type Local :雑誌掲載論文
ISSN :0007-1048
Publisher :Blackwell Publishing
URI :http://hdl.handle.net/20.500.12000/2608
Citation :British journal of haematology Vol.136 no.3 p.424 -432
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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