Cationic antimicrobial peptide CC34 potential anticancer and apoptotic induction on cancer cells

IF 2.4 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Liqiang Dong, Yunhe Li, Yaguang Zhang, Shi Su
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Abstract

To evaluate the potential of antimicrobial peptide CC34 for use as therapeutic agents for gastric cancer SGC-7901 and hepatocellular carcinoma HepG-2. In this study, the antibacterial activity and antibacterial mechanism were tested by the minimum inhibitory concentration (MIC) analysis, minimal bactericidal concentration (MBC) analysis, bacterial biofilm and NaCl permeability assays. Then, we assessed the hemolytic activity and cytotoxicity of CC34 for red blood cells and cancer cells, respectively. Apoptosis assay, cell cycle analysis, determination of intracellular ROS, western blot analysis caspase activity assay and ATP assay were further performed to investigate the mechanism of CC34 affected cancer cells. The novel peptide could inhibit Gram-negative and Gram-positive bacteria, with low hemolytic activity against mouse and chicken erythrocytes. Moreover, CC34 exhibited higher inhibitory activity against biofilm formation. In addition, our data showed that CC34 significantly suppressed cell proliferation, in a dose dependent manner. CC34 induced apoptosis, induced reactive oxygen species (ROS) generation, inhibited B-cell lymphoma-2 (Bcl-2) expression, increase B-cell lymphoma protein 2 associated X protein (Bax) expression, release of cytochrome c (Cyt C), promoted caspase-3 and − 9 activities and reduced cellular ATP levels in cancer cells. Our results indicate that CC34 with antimicrobial activity have a highly potent ability to induced apoptosis via mitochondrial-mediated apoptotic pathway in cancer cells.

阳离子抗菌肽CC34对癌细胞的潜在抗癌和诱导凋亡作用
目的:评价抗菌肽CC34作为胃癌SGC-7901和肝癌HepG-2治疗药物的潜力。通过最低抑菌浓度(MIC)分析、最低杀菌浓度(MBC)分析、细菌生物膜和NaCl渗透性测试,对其抑菌活性和抑菌机制进行了研究。然后,我们分别评估了CC34对红细胞和癌细胞的溶血活性和细胞毒性。通过细胞凋亡、细胞周期分析、细胞内ROS测定、western blot分析、caspase活性测定、ATP测定等方法探讨CC34影响癌细胞的作用机制。该肽对革兰氏阴性菌和革兰氏阳性菌均有抑制作用,对小鼠和鸡红细胞的溶血活性较低。此外,CC34对生物膜的形成具有较高的抑制活性。此外,我们的数据显示CC34以剂量依赖的方式显著抑制细胞增殖。CC34诱导癌细胞凋亡,诱导活性氧(ROS)生成,抑制b细胞淋巴瘤-2 (Bcl-2)表达,增加b细胞淋巴瘤蛋白2相关X蛋白(Bax)表达,细胞色素c (Cyt c)释放,促进caspase-3和- 9活性,降低细胞ATP水平。我们的研究结果表明,具有抗菌活性的CC34具有通过线粒体介导的凋亡途径诱导癌细胞凋亡的强大能力。
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来源期刊
Amino Acids
Amino Acids 生物-生化与分子生物学
CiteScore
6.40
自引率
5.70%
发文量
99
审稿时长
2.2 months
期刊介绍: Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered. Fields of interest include: Biochemistry, food chemistry, nutrition, neurology, psychiatry, pharmacology, nephrology, gastroenterology, microbiology
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