Mo-CBP3-PepIII altera o perfil proteômico de células de câncer gástrico, induz a formação de poros na membrana e o acúmulo excessivo de ROS

Abstract

Plant-derived peptides have gained prominence due to the possibility of structural modifications and selective toxicity. Moringa oleifera gave rise to the peptide Mo-CBP3-PepIII, which was synthesized to achieve greater selectivity. Initially, it was investigated for its antimicrobial and antifungal activities; therefore, the promising results led to further analyses regarding its antitumor potential. In this study, its activity against gastric adenocarcinoma cells (AGS) was evaluated, demonstrating low toxicity toward normal gastric mucosal cells (MNP-01). The mechanism of action of the synthetic peptide was investigated. First, cytotoxicity analysis was performed to determine the IC₅₀ value, followed by the evaluation of membrane integrity, accumulation of reactive oxygen species, morphological alterations by scanning electron microscopy, and proteomic analysis. Proteomic profiling revealed that the peptide modulated proteins involved in proliferation, metabolism, cytoskeletal organization, stress response, cellular repair, and drug resistance. A reduction in the expression of pro-tumoral proteins essential for cancer development and survival was observed, while an increase in the abundance of some tumor suppressor proteins was detected. The peptide promoted increased cellular vulnerability to oxidative stress, an important mechanism in tumor cell lysis. Proteomic analysis highlighted a reduction in proteins highly associated with resistance to several therapies, such as CLIC1 and HNRNPC, whose downregulation is related to decreased resistance to cisplatin, oxaliplatin, and vincristine. Conversely, some proteins showed increased abundance, including TXNL1, which contributed to reduced resistance to cisplatin. These findings indicate a gastric antitumor effect with a multifaceted mechanism of action, involving increased membrane permeability, pore formation, and dysregulation of multiple intracellular pathways, suggesting that Mo-CBP3-PepIII is a promising therapeutic candidate, either alone or in combination with conventional drugs. Therefore, future studies should further elucidate its effects on apoptosis, migration, tumor invasion, and associated signaling pathways, as well as deepen the investigation of the proteins identified in this study to better understand their roles in tumor biology and the potential interaction of Mo-CBP3-PepIII with conventional chemotherapeutic agents.