The cathelicidin-BF Lys16 mutant Cbf-K16 selectively inhibits non-small cell lung cancer proliferation in vitro

  • Authors:
    • Yuwei Tian
    • Hui Wang
    • Bing Li
    • Mengyun Ke
    • Jing Wang
    • Jie Dou
    • Changlin Zhou
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  • Published online on: August 23, 2013     https://doi.org/10.3892/or.2013.2693
  • Pages: 2502-2510
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Abstract

The 30-amino acid antimicrobial peptide Cbf-K16 is a cathelicidin-BF (BF-30) Lys16 mutant derived from the snake venom of Bungarus fasciatus. Our previous study found that BF-30 selectively inhibited the proliferation of the metastatic melanoma cell line B16F10 in vitro and in vivo, but had a negligible effect on human lung cells. In the present study, it was demonstrated for the first time that Cbf-K16 selectively inhibits the proliferation of lung carcinoma cells in vitro, with low toxicity to normal cells. The half-maximal inhibitory concentrations (IC50) of Cbf-K16 against H460 human non-small cell lung carcinoma cells and mouse Lewis lung cancer cells were only 16.5 and 10.5 µM, respectively, which were much less compared to that of BF-30 (45 and 40.3 µM). Data using a transmission electron microscope (TEM) assay showed that, at 20 and 40 µM, Cbf-K16 induced the rupture of the cytoplasmic membrane, which was consistent with data obtained from lactate dehydrogenase (LDH) release assays. The LDH release increased from 17.8 to 52.9% as the duration and dosage of Cbf-K16 increased. Annexin V-fluorescein and propidium iodide staining assays indicated that there were no obvious apoptotic effects at the different dosages and times tested. In H460 cells, the rate of genomic DNA binding increased from 51.9 to 86.8% as the concentration of Cbf-K16 increased from 5 to 10 µM. These data indicate that Cbf-K16 selectively inhibits the proliferation of lung carcinoma cells via cytoplasmic membrane permeabilization and DNA binding, rather than apoptosis. Although Cbf-K16 displayed significant cytotoxic activity (40 µM) against tumor cells, in splenocytes no significant inhibitory effect was observed and hemolysis was only 5.6%. These results suggest that Cbf-K16 is a low-toxicity anti-lung cancer drug candidate.
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November 2013
Volume 30 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Tian Y, Wang H, Li B, Ke M, Wang J, Dou J and Zhou C: The cathelicidin-BF Lys16 mutant Cbf-K16 selectively inhibits non-small cell lung cancer proliferation in vitro. Oncol Rep 30: 2502-2510, 2013.
APA
Tian, Y., Wang, H., Li, B., Ke, M., Wang, J., Dou, J., & Zhou, C. (2013). The cathelicidin-BF Lys16 mutant Cbf-K16 selectively inhibits non-small cell lung cancer proliferation in vitro. Oncology Reports, 30, 2502-2510. https://doi.org/10.3892/or.2013.2693
MLA
Tian, Y., Wang, H., Li, B., Ke, M., Wang, J., Dou, J., Zhou, C."The cathelicidin-BF Lys16 mutant Cbf-K16 selectively inhibits non-small cell lung cancer proliferation in vitro". Oncology Reports 30.5 (2013): 2502-2510.
Chicago
Tian, Y., Wang, H., Li, B., Ke, M., Wang, J., Dou, J., Zhou, C."The cathelicidin-BF Lys16 mutant Cbf-K16 selectively inhibits non-small cell lung cancer proliferation in vitro". Oncology Reports 30, no. 5 (2013): 2502-2510. https://doi.org/10.3892/or.2013.2693