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 -