title: IGF1R tyrosine kinase inhibitor enhances the cytotoxic effect of methyl jasmonate in endometrial cancer.
abstract: The present study evaluated the cytotoxic activity of methyl jasmonate (MJ) in endometrial cancer cells and examined the hypothesis that the apoptotic and anti-proliferative actions of MJ in these cell lines can be enhanced by co-targeting the insulin-like growth factor-1 receptor (IGF1R) signaling pathway. MJ had a potent pro-apoptotic effect and exhibited significant toxicity in all cell lines tested. MJ in combination with NVP-AEW541, a selective IGF1R tyrosine kinase inhibitor, had significantly increased cytotoxicity. MJ decreased IGF1R phosphorylation, however, it enhanced AKT phosphorylation and abolished the anti-apoptotic effect of IGF1. These findings suggest that combined IGF1R inhibitor and MJ administration may constitute an attractive modality for treating endometrial cancer.
authors.affiliation: Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba 44281, Israel. Electronic address: ilan.bruchim@gmail.com.
authors.forename: Ilan
authors.initials: I
authors.lastname: Bruchim
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Rive
authors.initials: R
authors.lastname: Sarfstein
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Reiss
authors.affiliation: Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Flescher
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Werner
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D054883:Oxylipins / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000085:Acetates; D003517:Cyclopentanes; C501177:NVP-AEW541; D054883:Oxylipins; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C072239:methyl jasmonate; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Endometrial carcinoma; IGF1 receptor (IGF1R); Insulin-like growth factor-1 (IGF1); Methyl jasmonate; NVP-AEW541; Uterine serous carcinoma