Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
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Increased Chemotherapeutic Activity of Camptothecin in Cancer Cells by siRNA-Induced Silencing of WRN Helicase
Kazunobu FutamiMotoki TakagiAkira ShimamotoMasanobu SugimotoYasuhiro Furuichi
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2007 Volume 30 Issue 10 Pages 1958-1961

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Abstract

Werner syndrome helicase (WRN) participates in a wide range of DNA activities, including replication, double-strand DNA break repair, telomere and retrovirus long terminal repeat maintenance. Mutations of the WRN gene cause Werner syndrome (WS), an autosomal recessive premature ageing disorder associated with various symptoms related to ageing. In this study, we investigated the siRNA that specifically down-regulates WRN expression. WRN silencing increased markedly the chemotherapeutic activity of camptothecin (CPT) on cancer cells in terms of the extent of efficacy and lowering effective drug dosage, accompanied by suppressing recovery from DNA damage caused by CPT. Here, we propose a potential combination therapy of WRN-siRNA and CPT, looking forward to minimizing the inevitable adverse effects associated with cancer chemotherapy.

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© 2007 The Pharmaceutical Society of Japan
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