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Open AccessArticle

Colicin N Mediates Apoptosis and Suppresses Integrin-Modulated Survival in Human Lung Cancer Cells

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Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Vaccines and Therapeutic Proteins Research Group, the Special Task Force for Activating Research (STAR), Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Department of Pharmacy, School of Health Care Professions, University of San Carlos, Cebu 6000, Philippines
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Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Cell-based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
*
Authors to whom correspondence should be addressed.
Molecules 2020, 25(4), 816; https://doi.org/10.3390/molecules25040816 (registering DOI)
Received: 15 January 2020 / Revised: 6 February 2020 / Accepted: 12 February 2020 / Published: 13 February 2020
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. View Full-Text
Keywords: Colicins; Apoptosis; Integrin; selective anticancer; human lung cancer cells Colicins; Apoptosis; Integrin; selective anticancer; human lung cancer cells
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MDPI and ACS Style

Arunmanee, W.; Ecoy, G.A.U.; Khine, H.E.E.; Duangkaew, M.; Prompetchara, E.; Chanvorachote, P.; Chaotham, C. Colicin N Mediates Apoptosis and Suppresses Integrin-Modulated Survival in Human Lung Cancer Cells. Molecules 2020, 25, 816.

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