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The investigation of ceranib-2 on apoptosis and drug interaction with carboplatin in human non small cell lung cancer cells in vitro

Yildiz-Ozer, Merve; Oztopcu-Vatan, Pinar; Kus, Gokhan


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        "affiliation": "Eskisehir Osmangazi Univ, Grad Sch Nat & Appl Sci, Eskisehir, Turkey", 
        "name": "Yildiz-Ozer, Merve"
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      {
        "affiliation": "Eskisehir Osmangazi Univ, Fac Arts & Sci, Dept Biol, Eskisehir, Turkey", 
        "name": "Oztopcu-Vatan, Pinar"
      }, 
      {
        "affiliation": "Anadolu Univ, Open Fac, Dept Hlth Programme, Eskisehir, Turkey", 
        "name": "Kus, Gokhan"
      }
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    "description": "Ceramide is found to be involved in inhibition of cell division and induction of apoptosis in certain tumour cells. Ceranib-2 is an agent that increases ceramide levels by inhibiting ceramidase in cancer cells. Therefore, we aimed to investigate the effects of ceranib-2 on cell survival, apoptosis and interaction with carboplatin in human non-small cell lung cancer cells. The cytotoxic effect of ceranib-2 (1-100 A mu M) was determined by MTT assay in human lung adenocarcinoma (A549) and large cell lung carcinoma (H460) cells. Carboplatin (1-100 A mu M) and lung bronchial epithelial cells (BEAS-2B) were used as positive controls. Morphological and ultrastructural changes were analysed by light microscope and TEM. Apoptotic/necrotic cell death and acid ceramidase activity were analysed by ELISA. Combination effects of ceranib-2 and carboplatin were investigated by MTT. The expression levels of CASP3, CASP9, BAX and BCL-2 were examined by qRT-PCR. The IC50 of ceranib-2 was determined as 22 mu M in A549 cells and 8 mu M in H460 cells for 24 h. Morphological changes and induction of DNA fragmentation have revealed apoptotic effects of ceranib-2 in both cell lines. Ceranib-2 and carboplatin has shown synergism in combined treatment at 10 and 25 mu M doses in H460 cells for 24 h. Ceranib-2 inhibited acid ceramidase activity by 44% at 25 A mu M in H460 cells. Finally, CASP3, CASP9 and BAX expressions were increased while BCL-2 expression was reduced in both cells. Our results obtained some preliminary results about the cytotoxic and apoptotic effects of ceranib-2 for the first time in NSCLC cell lines.", 
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      "issue": "1", 
      "pages": "387-396", 
      "title": "CYTOTECHNOLOGY", 
      "volume": "70"
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