title: Nimbolide inhibits IGF-I-mediated PI3K/Akt and MAPK signalling in human breast cancer cell lines (MCF-7 and MDA-MB-231).
abstract: The insulin-like growth factor I (IGF-I) signalling pathway contributes a major role on various cancer cell proliferation, survival and cell cycle. The present study was aimed to investigate the effect of nimbolide on IGF signalling and cell cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines. The protein expression of IGF signalling molecules and cell cycle protein levels was assessed by western blot analysis. In order to study the interaction of nimbolide on IGF-1 signalling pathway, IGF-I and phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) were used to treat MCF-7 and MDA-MB-231 cells. Further, the cell cycle arrest was analysed by flow cytometry. The protein expression of IGF signalling molecules was significantly decreased in nimbolide-treated breast cancer cells. PI3K inhibitor and IGF-I with nimbolide treatment notably inhibited phosphorylated Akt. The cell cycle arrest was observed at the G0/G1 phase, and accumulation of apoptotic cells was observed in nimbolide-treated breast cancer cell lines. Nimbolide also increased the protein expression of p21 and decreased the cyclins in both the cell lines. Nimbolide decreases the proliferation of breast cancer cells by modulating the IGF signalling molecules, which could be very useful for the breast cancer treatment.
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Elumalai
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Arunkumar
authors.forename: Chellakkan Selvanesan
authors.initials: CS
authors.lastname: Benson
authors.forename: Govindaraj
authors.initials: G
authors.lastname: Sharmila
authors.forename: Jagadeesan
authors.initials: J
authors.lastname: Arunakaran
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D036701:Limonins / Q000494:pharmacology*; D061986:MCF-7 Cells; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002867:Chromones; D055504:Insulin Receptor Substrate Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D036701:Limonins; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D016271:Proto-Oncogene Proteins c-myc; D017526:Receptor, IGF Type 1; D051176:beta Catenin; C515497:IGFBP3 protein, human; C526297:IRS2 protein, human; C489427:MYC protein, human; C042198:nimbolide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494929:PTEN protein, human
keywords: IGF-I signalling; breast cancer; cell cycle; cell proliferation; nimbolide