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

• Hosokawa Mika

  Department of Pharmaceutics, Kobe Pharmaceutical University

• Tanaka Shota

  Department of Pharmaceutics, Kobe Pharmaceutical University

• Ueda Kumiko

  Department of Pharmaceutics, Kobe Pharmaceutical University

• Iwakawa Seigo

  Department of Pharmaceutics, Kobe Pharmaceutical University

Abstract

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.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 40 (12), 2199-2204, 2017

  The Pharmaceutical Society of Japan

Keywords

• schedule-dependent treatment
• epigenetic therapy
• colorectal cancer
• DNA methyltransferase inhibitor
• histone deacetylase inhibitor

Details

• CRID: 1390282679608263936
• NII Article ID: 130006235432
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b17-00439
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 028676346
• PubMed: 28954936
• Web Site: http://id.ndl.go.jp/bib/028676346
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I028676346
• Web Site: https://www.jstage.jst.go.jp/article/bpb/40/12/40_b17-00439/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2018244020
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed