Journal Title
Title of Journal: Invest New Drugs
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Abbravation: Investigational New Drugs
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Authors: Raquel C Maia Flavia C Vasconcelos Thiago de Sá Bacelar Eduardo J Salustiano Luis Felipe R da Silva Débora L Pereira Arthur MoellmanCoelho Chaquip D Netto Alcides J da Silva Vivian M Rumjanek Paulo R R Costa
Publish Date: 2010/05/25
Volume: 29, Issue: 6, Pages: 1143-1155
Abstract
Despite the relevant therapeutic progresses obtained with imatinib clinical resistance to this drug has emerged and reemerged after cytogenetic remission in a group of patients with chronic myeloid leukemia CML Therefore novel treatment strategies are needed In this study we evaluated the antiCML activity and mechanisms of action of LQB118 a pterocarpanquinone structurally related to lapachol 2hydroxy33methyl2butenyl14naphthoquinone LQB118 treatment resulted in an important reduction of cell viability in cell lines derived from CML both the vincristinesensitive K562 cell line and the resistant K562Lucena a cell line overexpressing Pglycoprotein In agreement with these results the induction of caspase3 activation by this compound indicated that a significant rate of apoptosis was taking place In these cell lines apoptosis induced by LQB118 was accompanied by a reduction of Pglycoprotein survivin and XIAP expression Moreover this effect was not restricted to cell lines as LQB118 produced significant apoptosis rate in cells from CML patients exhibiting multifactorial drug resistance phenotype such as Pglycoprotein MRP1 and p53 overexpression The data suggest that LQB118 has a potent antiCML activity that can overcome multifactorial drug resistance mechanisms making this compound a promising new antiCML agent
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