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

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Yildiz-Ozer M., Oztopcu-Vatan P., KUŞ G.

CYTOTECHNOLOGY, vol.70, no.1, pp.387-396, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 70 Issue: 1
  • Publication Date: 2018
  • Doi Number: 10.1007/s10616-017-0154-8
  • Journal Name: CYTOTECHNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.387-396
  • Keywords: Ceranib-2, Ceramidase inhibitor, Cytotoxicity, Apoptosis, Combined therapy, ACID CERAMIDASE, SPHINGOSINE, RESISTANCE, PATHWAY, PROLIFERATION, SPHINGOLIPIDS, REGULATORS
  • Anadolu University Affiliated: Yes


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.