Barragán-Cárdenas Andrea, Urrea-Pelayo Maribel, Niño-Ramírez Víctor Alfonso, Umaña-Pérez Adriana, Vernot Jean Paul, Parra-Giraldo Claudia Marcela, Fierro-Medina Ricardo, Rivera-Monroy Zuly, García-Castañeda Javier
Facultad de Ciencias, Universidad Nacional de Colombia Carrera 45 No 26-85, Building 451, Office 334 11321 Bogotá Colombia
Facultad de Medicina, Departamento de Ciencias fisiológicas, Universidad Nacional de Colombia Carrera 45 No 26-85 11321 Bogotá Colombia.
RSC Adv. 2020 May 6;10(30):17593-17601. doi: 10.1039/d0ra02688c. eCollection 2020 May 5.
The cytotoxic effect against the breast cancer cell line MDA-MB-468 of the palindromic peptide LfcinB (21-25): RWQWRWQWR and its analogous peptides, obtained alanine scanning, was evaluated. The results indicate that the palindromic peptide exhibited a concentration-dependent cytotoxic effect against this cell line. The cytotoxic effect of the palindromic peptide was fast and selective and was sustained for up to 48 h of treatment. MDA-MB-468 cells treated with the palindromic peptide exhibited severe cellular damage, acquiring rounded forms and shrinkage, a behavior typical of apoptotic events. The analogous peptides exhibited fewer cytotoxic effects than the original palindromic peptide, suggesting that the substitution of any amino acid with alanine diminishes the cytotoxic effect. The Arg and Trp residues proved to be the most relevant for the cytotoxic effect; the analogous peptides with substitutions of Trp with Ala did not induce a change in cellular morphology, while analogous peptides with substitutions of Arg or Gln with Ala induced cellular damage. Also, neither the palindromic peptide nor its analogues exerted a significant cytotoxic effect on normal fibroblasts, indicating that the peptides had a selective cytotoxic effect on cancerous cells. The peptide LfcinB (21-25), and its analogues exhibited antibacterial activity against and strains and a selective cytotoxic effect against the breast cancer cell line MDA-MB-468.
评估了回文肽LfcinB(21 - 25)：RWQWRWQWR及其通过丙氨酸扫描获得的类似肽对乳腺癌细胞系MDA - MB - 468的细胞毒性作用。结果表明，该回文肽对该细胞系表现出浓度依赖性细胞毒性作用。回文肽的细胞毒性作用迅速且具有选择性，在长达48小时的处理过程中持续存在。用回文肽处理的MDA - MB - 468细胞表现出严重的细胞损伤，呈现圆形并收缩，这是凋亡事件的典型行为。类似肽表现出比原始回文肽更少的细胞毒性作用，表明用丙氨酸取代任何氨基酸都会降低细胞毒性作用。结果证明，Arg和Trp残基对细胞毒性作用最为关键；用Ala取代Trp的类似肽未引起细胞形态变化，而用Ala取代Arg或Gln的类似肽则诱导细胞损伤。此外，回文肽及其类似物对正常成纤维细胞均未产生显著的细胞毒性作用，表明这些肽对癌细胞具有选择性细胞毒性作用。肽LfcinB(21 - 25)及其类似物对 和 菌株表现出抗菌活性，并对乳腺癌细胞系MDA - MB - 468具有选择性细胞毒性作用。
