Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma

Lucio Tentori, Carlo Leonetti, Marco Scarsella, Alessia Muzi, Emanuela Mazzon, Matteo Vergati, Olindo Forini, Rena Lapidus, Weizheng Xu, Annalisa Susanna Dorio, Jie Zhang, Salvatore Cuzzocrea, Grazia Graziani

Research output: Contribution to journalArticle

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the antitumor activity of the topoisomerase I inhibitor irinotecan (CPT-11), which is used to treat advanced colorectal carcinoma. Since PARP inhibitors sensitize tumor cells also to the methylating agent temozolomide (TMZ) and clinical trials are evaluating CPT-11 in combination with TMZ, we tested whether the PARP inhibitor GPI 15427 (10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de] anthracen-3-one) increases the efficacy of CPT-11 + TMZ against colon cancer. Moreover, due to the ability of PARP inhibitors to avoid cell death consequent to PARP-1 overactivation, we evaluated whether oral administration of GPI 15427 provides protection from the dose-limiting intestinal toxicity of CPT-11. The results of colony formation assay indicated that GPI 15427 increased the antiproliferative effects (combination index

Original languageEnglish
JournalFASEB Journal
Volume20
Issue number10
DOIs
Publication statusPublished - Aug 2006

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Keywords

  • Cancer
  • Chemotherapy
  • Diarrhea
  • Mucositis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Tentori, L., Leonetti, C., Scarsella, M., Muzi, A., Mazzon, E., Vergati, M., Forini, O., Lapidus, R., Xu, W., Dorio, A. S., Zhang, J., Cuzzocrea, S., & Graziani, G. (2006). Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma. FASEB Journal, 20(10). https://doi.org/10.1096/fj.06-5916fje