Abstract
The inherent limitations, including serious side-effects and drug resistance, of current chemotherapies necessitate the search for alternative treatments especially for lung cancer. Herein, the anticancer activity of colicin N, bacteria-produced antibiotic peptide, was investigated in various human lung cancer cells. After 24 h of treatment, colicin N at 5–15 µM selectively caused cytotoxicity detected by MTT assay in human lung cancer H460, H292 and H23 cells with no noticeable cell death in human dermal papilla DPCs cells. Flow cytometry analysis of annexin V-FITC/propidium iodide indicated that colicin N primarily induced apoptosis in human lung cancer cells. The activation of extrinsic apoptosis evidenced with the reduction of c-FLIP and caspase-8, as well as the modulation of intrinsic apoptosis signaling proteins including Bax and Mcl-1 were observed via Western blot analysis in lung cancer cells cultured with colicin N (10–15 µM) for 12 h. Moreover, 5–15 µM of colicin N down-regulated the expression of activated Akt (p-Akt) and its upstream survival molecules, integrin β1 and αV in human lung cancer cells. Taken together, colicin N exhibits selective anticancer activity associated with suppression of integrin-modulated survival which potentiate the development of a novel therapy with high safety profile for treatment of human lung cancer.
Highlights
Cancer is a global health burden and non-small cell lung carcinoma (NSCLC) is the primary cause of cancer-related deaths worldwide [1]
Colicin N comprising all domains was successfully expressed in E. coli BL21-AI from a plasmid encoding a C-terminal Histidine-tagged Colicin N gene in a pET3a vector
The bactericidal activity against E. coli tested by broth microdilution method was demonstrated to evaluate a biological function of the expressed colicin N
Summary
Cancer is a global health burden and non-small cell lung carcinoma (NSCLC) is the primary cause of cancer-related deaths worldwide [1]. Clinical and in vitro evidence indicate that lung cancer cells. To seek novel anticancer drugs, the current paradigm holds that anticancer agents induce toxicity in cancer cells through restoration of normal apoptosis signals [5,6,7]. To restore normal apoptosis signals, in vivo and in vitro studies show that suppression of anti-apoptosis Bcl-2 (B-cell lymphoma 2) and Mcl-1 (Myeloid cell leukemia 1) protein as well as up-regulation of pro-apoptosis protein, Bax (Bcl-2-associated X protein) strongly correlates with apoptosis induction in cancer cells, including those obtained from advanced grade lung cancer specimens [9,10].
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