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 › peer-review

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

Keywords

Cancer
Chemotherapy
Diarrhea
Mucositis

ASJC Scopus subject areas

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

Access to Document

10.1096/fj.06-5916fje

Fingerprint Dive into the research topics of 'Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma'. Together they form a unique fingerprint.

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 › peer-review

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.

@article{deecb918285649668791f38613c60e09,

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

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 ",

keywords = "Cancer, Chemotherapy, Diarrhea, Mucositis",

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

year = "2006",

month = aug,

doi = "10.1096/fj.06-5916fje",

language = "English",

volume = "20",

journal = "FASEB Journal",

issn = "0892-6638",

publisher = "FASEB",

number = "10",

}

TY - JOUR

T1 - Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma

AU - Tentori, Lucio

AU - Leonetti, Carlo

AU - Scarsella, Marco

AU - Muzi, Alessia

AU - Mazzon, Emanuela

AU - Vergati, Matteo

AU - Forini, Olindo

AU - Lapidus, Rena

AU - Xu, Weizheng

AU - Dorio, Annalisa Susanna

AU - Zhang, Jie

AU - Cuzzocrea, Salvatore

AU - Graziani, Grazia

PY - 2006/8

Y1 - 2006/8

N2 - 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

AB - 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

KW - Cancer

KW - Chemotherapy

KW - Diarrhea

KW - Mucositis

UR - http://www.scopus.com/inward/record.url?scp=33845672155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845672155&partnerID=8YFLogxK

U2 - 10.1096/fj.06-5916fje

DO - 10.1096/fj.06-5916fje

M3 - Article

C2 - 16809434

AN - SCOPUS:33845672155

VL - 20

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 10

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this