Mesquita Felipe P, de Oliveira Francisco L, da Silva Emerson L, Brito Daiane M S, de Moraes Maria E A, Souza Pedro F N, Montenegro Raquel C
Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, CE 60430-275, Brazil.
Cearense Foundation to Support Scientific and Technological Development, Fortaleza 60822-131, Brazil.
ACS Omega. 2024 Oct 11;9(42):43252-43263. doi: 10.1021/acsomega.4c08194. eCollection 2024 Oct 22.
Cancer resistance to drugs and chemotherapy is a problem faced by public health systems worldwide. Repositioning antimicrobial peptides could be an efficient strategy to overcome that problem. This study aimed at repurposing antimicrobial peptides PepGAT and PepKAA for cancer treatment. After screening against several cancers, PepGAT and PepKAA presented IC50 values of 125.42 and 40.51 μM at 72 h toward colorectal cancer (CRC) cells. The mechanisms of action revealed that both peptides induced cell cycle arrest in G2/M and drove HCT-116 cells to death by triggering apoptosis. qPCR analysis revealed that peptides modulated gene expression in apoptosis, corroborating the data from caspase 3/7 and flow cytometry experiments. Yet, peptides induced ROS overaccumulation and increased membrane permeabilization, pore formation, and loss of internal content, leading to death. Additionally, peptides were able to inhibit cell invasion. Previous studies from the same group attested to no toxicity to normal human cells. Thus, PepGAT and PepKAA have great potential as anticancer molecules.
癌症对药物和化疗的耐药性是全球公共卫生系统面临的一个问题。重新利用抗菌肽可能是克服这一问题的有效策略。本研究旨在将抗菌肽PepGAT和PepKAA重新用于癌症治疗。在对几种癌症进行筛选后，PepGAT和PepKAA在72小时时对结直肠癌（CRC）细胞的IC50值分别为125.42和40.51μM。作用机制表明，这两种肽均诱导细胞周期停滞在G2/M期，并通过触发细胞凋亡促使HCT-116细胞死亡。qPCR分析表明，这些肽调节细胞凋亡中的基因表达，这与caspase 3/7和流式细胞术实验的数据一致。然而，这些肽诱导活性氧过度积累，并增加膜通透性、孔形成和内部内容物的丧失，从而导致细胞死亡。此外，这些肽能够抑制细胞侵袭。同一研究小组之前的研究证明其对正常人类细胞无毒性。因此，PepGAT和PepKAA作为抗癌分子具有巨大潜力。
