Cruz-Chamorro Lidia, Puertollano María A, Puertollano Elena, de Cienfuegos Gerardo Alvarez, de Pablo Manuel A
Unit of Microbiology, Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, E-23071 Jaén, Spain.
Peptides. 2006 Jun;27(6):1201-9. doi: 10.1016/j.peptides.2005.11.008. Epub 2005 Dec 13.
Antimicrobial peptides have received increasing attention not only as potential candidates to their administration as antimicrobial agents, but also as potential drugs applied in cancer therapy. Here, we have examined the action of both nisin and magainin on human promyelocytic leukemia HL-60 cells. Cells were cultured in presence of either nisin or magainin 1 as well as in combination with both nisin and magainin 1. Results have revealed that magainin, but not nisin, produces a loss of cell viability in HL-60 cells, and a minor increase of hemolysis, whereas it is not responsible for cell membrane disruption and lactate dehydrogenase (LDH) leakage. In addition, magainin is involved in a significant generation of reactive oxygen species (ROS), as well as in an augment of caspase-3 activity. Magainin-induced apoptosis was verified by DNA fragmentation and annexin V-FITC/propidium iodide (PI) staining of the cells. Promotion of cell death by magainin occurs via cytochrome c release accompanied by a substantial increase of proteasome activity. These results underline the importance of magainin as a drug capable of exerting an in vitro antitumoral activity by triggering apoptosis.
抗菌肽不仅作为抗菌剂给药的潜在候选物受到越来越多的关注，而且作为应用于癌症治疗的潜在药物也备受关注。在此，我们研究了乳链菌肽和蛙皮素对人早幼粒细胞白血病HL-60细胞的作用。细胞在乳链菌肽或蛙皮素1存在的情况下培养，以及在乳链菌肽和蛙皮素1联合存在的情况下培养。结果表明，蛙皮素而非乳链菌肽会导致HL-60细胞活力丧失，并使溶血略有增加，而它不会导致细胞膜破坏和乳酸脱氢酶（LDH）泄漏。此外，蛙皮素参与了活性氧（ROS）的大量产生，以及半胱天冬酶-3活性的增强。通过DNA片段化和细胞的膜联蛋白V-异硫氰酸荧光素/碘化丙啶（PI）染色证实了蛙皮素诱导的细胞凋亡。蛙皮素促进细胞死亡是通过细胞色素c释放伴随着蛋白酶体活性的大幅增加而发生的。这些结果强调了蛙皮素作为一种能够通过触发细胞凋亡发挥体外抗肿瘤活性的药物的重要性。
