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短小芽孢杆菌 Brevilaterin C 的广谱细胞毒性及其对人表皮癌细胞的特定作用机制。

Broad-spectrum cytotoxicity to cancer cells of Brevilaterin C from Brevibacillus laterosporus and its specific mechanism on human epidermal cancer cells.

机构信息

Lab of Enzyme Engineering, School of Food and Health, Beijing Technology and Business University, Beijing, Haidian District, China.

出版信息

J Cell Biochem. 2022 Jul;123(7):1237-1246. doi: 10.1002/jcb.30280. Epub 2022 Jun 3.

Abstract

Antimicrobial peptides (AMP) from Brevibacillus laterosporus have good prospects as clinical treatments for cancer. Nevertheless, details about their anticancer spectrum and mode of cytotoxicity remain poorly understood. A newly found AMP (named Brevilaterin C) secreted by B. laterosporus S62-9 exhibited strong inhibition on almost cancer cell lines examined at a concentration of 8 µg/ml but was relatively safe for normal cells. We further systematically examined its cytotoxicity and mechanism toward human epidermal cancer cell A431. A dosage of 3 µg/ml of Brevilaterin C could significantly increase lactate dehydrogenase release of tumor cells. Moreover, it could remarkably increase the ratio of apoptosis and reactive oxygen species generation of A431, indicating effective induction of apoptosis. Moreover, the formation of JC-1 aggregates was effectively prevented by a low concentration of Brevilaterin C, indicating its effective induction of A431's apoptosis. Brevilaterin C exhibited broad-spectrum cytotoxicity to cancer cells, indicating a good potential prospect in the medical field.

摘要

短芽孢杆菌来源的抗菌肽(AMP)有望成为癌症的临床治疗方法。然而,关于其抗癌谱和细胞毒性模式的细节仍知之甚少。短芽孢杆菌 S62-9 分泌的一种新发现的 AMP(命名为 Brevilaterin C)在 8μg/ml 的浓度下对几乎所有检测的癌细胞系均表现出强烈的抑制作用,但对正常细胞相对安全。我们进一步系统地研究了它对人表皮癌细胞 A431 的细胞毒性及其作用机制。3μg/ml 的 Brevilaterin C 可显著增加肿瘤细胞乳酸脱氢酶的释放。此外,它可以显著增加 A431 的细胞凋亡和活性氧生成的比例,表明有效诱导细胞凋亡。此外,Brevilaterin C 可有效阻止 JC-1 聚集体的形成,表明其可有效诱导 A431 的细胞凋亡。Brevilaterin C 对癌细胞具有广谱细胞毒性,表明其在医学领域具有良好的应用前景。

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