title: Effects of flavopiridol on critical regulation pathways of CD133high/CD44high lung cancer stem cells.
abstract: BACKGROUND
  Flavopiridol a semisynthetic flavone that inhibits cyclin-dependent kinases (CDKs) and has growth-inhibitory activity and induces a blockade of cell-cycle progression at G1-phase and apoptosis in numerous human tumor cell lines and is currently under investigation in phase II clinical trials. Cancer stem cells (CSCs) are comprised of subpopulation of cells in tumors that have been proposed to be responsible for recurrence and resistance to chemotherapy. The aim of the present study was to investigate the effects of flavopiridol in cancer stem cell cytoskeleton, cell adhesion, and epithelial to mesenchymal transition in CSCs.
  
  
  METHODS
  The cells were treated with flavopiridol to determine the inhibitory effect. Cell viability and proliferation were determined by using the WST-1 assay. Caspase activity and immunofluorescence analyses were performed for the evaluation of apoptosis, cell cytoskeleton, and epithelial-mesenchymal transition (EMT) markers. The effects of flavopiridol on the cell cycle were also evaluated. Flow cytometric analysis was used to detect the percentages of CSCs subpopulation. We analyzed the gene expression patterns to predict cell cycle and cell cytoskeleton in CSCs by RT-PCR.
  
  
  RESULTS
  Flavopiridol-induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspases activity. Cell cycle analyses revealed that flavopiridol induces G1 phase cell cycle arrest. Flavopiridol significantly decreased the mRNA expressions of the genes that regulate the cell cytoskeleton and cell cycle components and cell motility in CSCs.
  
  
  CONCLUSIONS
  Our results suggest that Flavopiridol has activity against lung CSCs and may be effective chemotherapeutic molecule for lung cancer treatment.
authors: Department of Medical Biology, Ege University Faculty of Medicine, Izmir Department of Histology and Embryology, Yuzuncu Yil University Faculty of Medicine, Van Department of Histology and Embryology, Ege University Faculty of Medicine, Izmir, Turkey.
authors: Vildan
authors: V
authors: Bozok Cetintas
authors: Eda
authors: E
authors: Acikgoz
authors: Gurkan
authors: G
authors: Yigitturk
authors: Kenan
authors: K
authors: Demir
authors: Gulperi
authors: G
authors: Oktem
authors: Burçin
authors: B
authors: Tezcanli Kaymaz
authors: Fatih
authors: F
authors: Oltulu
authors: Huseyin
authors: H
authors: Aktug
mesh_terms: D000071916:AC133 Antigen / Q000187:drug effects / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology*; D016133:Polymerase Chain Reaction
chemical_list: D000071916:AC133 Antigen; D000970:Antineoplastic Agents; C497483:CD44 protein, human; D004273:DNA, Neoplasm; D005419:Flavonoids; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010880:Piperidines; C077990:alvocidib; D020169:Caspases