title: SiO2@antisense molecules covered by nepetalactone, extracted from Nepeta gloeocephala, inhibits ILK phosphorylation and downstream PKB/AKT signaling in HeLa cells.
abstract: In this study, the anticancer property of SiO2@antisense molecules (SiO2@AMs) and SiO2@AM covered by nepetalactone (SiO2@AM/CN), extracted from Nepeta gloeocephala, was investigated. Here integrin-linked kinase (ILK) phosphorylation and protein kinase B/AKT (PKB/AKT) signaling was studied when HeLa cells were exposed to SiO2@AM and SiO2@AM/CN. First, N. gloeocephala was identified at the Iranian National Herbarium. Then, its essential oil (EO) was obtained by the hydrodistillation method. In the next step, 4aα,7α,7aα-nepetalactone was extracted from the EO, based on the spectroscopic data. To obtain SiO2@AM/CN, 1 ml of SiO2@AM was mixed with extracted nepetalactone and then strongly shaken for 30 min. Finally, serial concentrations (100, 50, 25 and 12.5 μg ml-1) of SiO2@AM and SiO2@AM/CN were prepared and then exposed to HeLa cells (2 × 105cells per ml) for 24 h at 37 °C. After incubation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell-cycle analysis, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blots were carried out. To find ILK phosphorylation and PKB/AKT signaling, the expression of threonine-173 (Thr-173), serine-246 (Ser-246), total ILK, AKT-Ser473, AKT-Thr308 and total AKT was investigated. HeLa cells that were treated with SiO2@AM/CN had G2/M arrest. Based on the TUNEL assay, many apoptotic cells have been shown when they were exposed to SiO2@AM/CN. Importantly, SiO2@AM/CN decreased ILK phosphorylation at Thr-173 and Ser-246 without affecting total ILK levels. Moreover, SiO2@AM/CN decreased AKT-Ser473 and AKT-Thr308 phosphorylation without affecting total PKB/AKT protein.
authors.affiliation: Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Dehghany Ashkezary
authors.affiliation: Department of Medicine, Yazd Branch, Islamic Azad University, Yazd, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Aboee-Mehrizi
authors.affiliation: Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran.
authors.forename: P
authors.initials: P
authors.lastname: Moradi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000081004:Cyclopentane Monoterpenes; D003517:Cyclopentanes; D006367:HeLa Cells; D006801:Humans; D027521:Nepeta / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011753:Pyrones; D015398:Signal Transduction / Q000187:drug effects*; D012822:Silicon Dioxide / Q000737:chemistry; D000099200:Scaffold Protein ILK
chemical_list: D000081004:Cyclopentane Monoterpenes; D003517:Cyclopentanes; D010936:Plant Extracts; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011753:Pyrones; D012822:Silicon Dioxide; D000099200:Scaffold Protein ILK; C115644:nepetalactone