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

doi:10.1096/fj.06-5916fje

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 journal › Article

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 language	English
Journal	FASEB Journal
Volume	20
Issue number	10
DOIs	https://doi.org/10.1096/fj.06-5916fje
Publication status	Published - 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

Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma. / Tentori, Lucio; Leonetti, Carlo; Scarsella, Marco; Muzi, Alessia; Mazzon, Emanuela; Vergati, Matteo; Forini, Olindo; Lapidus, Rena; Xu, Weizheng; Dorio, Annalisa Susanna; Zhang, Jie; Cuzzocrea, Salvatore; Graziani, Grazia.

In: FASEB Journal, Vol. 20, No. 10, 08.2006.

Research output: Contribution to journal › Article

Tentori, L, Leonetti, C, Scarsella, M, Muzi, A, Mazzon, E, Vergati, M, Forini, O, Lapidus, R, Xu, W, Dorio, AS, 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, vol. 20, no. 10. https://doi.org/10.1096/fj.06-5916fje

Tentori, Lucio ; Leonetti, Carlo ; Scarsella, Marco ; Muzi, Alessia ; Mazzon, Emanuela ; Vergati, Matteo ; Forini, Olindo ; Lapidus, Rena ; Xu, Weizheng ; Dorio, Annalisa Susanna ; Zhang, Jie ; Cuzzocrea, Salvatore ; Graziani, Grazia. / Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma. In: FASEB Journal. 2006 ; Vol. 20, No. 10.

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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 ",

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10.1096/fj.06-5916fje