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

被引:22
|
作者
Arunmanee, Wanatchaporn [1 ,2 ]
Ecoy, Gea Abigail U. [1 ,3 ]
Khine, Hnin Ei Ei [1 ]
Duangkaew, Methawee [1 ,2 ]
Prompetchara, Eakachai [2 ,4 ,5 ]
Chanvorachote, Pithi [6 ,7 ]
Chaotham, Chatchai [1 ,7 ]
机构
[1] Chulalongkorn Univ, Fac Pharmaceut Sci, Dept Biochem & Microbiol, Bangkok 10330, Thailand
[2] Chulalongkorn Univ, Fac Pharmaceut Sci, Special Task Force Activating Res STAR, Vaccines & Therapeut Prot Res Grp, Bangkok 10330, Thailand
[3] Univ San Carlos, Sch Hlth Care Profess, Dept Pharm, Cebu 6000, Philippines
[4] Chulalongkorn Univ, Fac Med, Dept Lab Med, Bangkok 10330, Thailand
[5] Chulalongkorn Univ, Fac Med, Ctr Excellence Vaccine Res & Dev, Chula VRC, Bangkok 10330, Thailand
[6] Chulalongkorn Univ, Fac Pharmaceut Sci, Dept Pharmacol & Physiol, Bangkok 10330, Thailand
[7] Chulalongkorn Univ, Fac Pharmaceut Sci, Cell Based Drug & Hlth Prod Dev Res Unit, Bangkok 10330, Thailand
来源
MOLECULES | 2020年 / 25卷 / 04期
关键词
Colicins; Apoptosis; Integrin; selective anticancer; human lung cancer cells; DRUG-RESISTANCE; C-FLIP; EXPRESSION; BCL-2; PATHWAY; CARCINOMA; MCL-1; BAX; INTERNALIZATION; INHIBITION;
D O I
10.3390/molecules25040816
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu M 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 viaWestern blot analysis in lung cancer cells cultured with colicin N (10-15 mu M) for 12 h. Moreover, 5-15 mu M of colicin N down-regulated the expression of activated Akt (p-Akt) and its upstream survival molecules, integrin fi1 and ffV 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.
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页数:15
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