論文

査読有り
2017年12月

Different Schedule-Dependent Effects of Epigenetic Modifiers on Cytotoxicity by Anticancer Drugs in Colorectal Cancer Cells

BIOLOGICAL & PHARMACEUTICAL BULLETIN
  • Mika Hosokawa
  • ,
  • Shota Tanaka
  • ,
  • Kumiko Ueda
  • ,
  • Seigo Iwakawa

40
12
開始ページ
2199
終了ページ
2204
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1248/bpb.b17-00439
出版者・発行元
PHARMACEUTICAL SOC JAPAN

Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay. As epigenetic modifiers, 3 DNA methyltransferase (DNMT) inhibitors such as decitabine (DAC), azacytidine (AC), and zebularine (Zeb), and 3 histone deacetylase (HDAC) inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA) were used. Combination effects were analyzed by the isobologram method. SW480 cells showed the lowest sensitivity to the anticancer drugs 5-fluorouracil, SN-38 (the active form of irinotecan), and oxaliplatin. In SW480 cells, epigenetic modifiers other than VPA showed the most significant synergistic effects when used before anticancer drugs, while VPA showed synergistic effects in co- or post-treatment. In the 3 other CRC cells, synergistic effects were less frequent and weaker. The dose of anticancer drugs may be reduced by combining epigenetic modifiers in SW480 cells, which are less sensitive to anticancer drugs, unlike the more sensitive HT29, SW48, and HCT116 cell lines. These results provide useful information for understanding how to incorporate epigenetic modifiers into current CRC chemotherapy.

リンク情報
DOI
https://doi.org/10.1248/bpb.b17-00439
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28954936
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000417011700026&DestApp=WOS_CPL
ID情報
  • DOI : 10.1248/bpb.b17-00439
  • ISSN : 0918-6158
  • PubMed ID : 28954936
  • Web of Science ID : WOS:000417011700026

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