Pep5, a Fragment of Cyclin D2, Shows Antiparasitic Effects in Different Stages of the Trypanosoma cruzi Life Cycle and Blocks Parasite Infectivity

Abstract

Pep5 (WELVVLGKL) is a fragment of cyclin D2 that exhibits a 2-fold increase in the S phase of the HeLa cell cycle. When covalently bound to a cellpenetrating peptide (Pep5-cpp), the nonapeptide induces cell death in several tumor cells, including breast cancer and melanoma cells. Additionally, Pep5-cpp reduces the in vivo tumor volume of rat glioblastoma. Chagas disease, which is caused by the flagellated parasite Trypanosoma cruzi, is a neglected disease that occurs mainly in the Americas, where it is considered an important public health issue. Given that there are only two options for treating the disease, it is exceptionally crucial to search for new molecules with potential pharmacological action against the parasites. In this study, we demonstrate that Pep5-cpp induces cell death in epimastigote, trypomastigote, and amastigote forms of T. cruzi. The Pep5-cpp peptide was also able to decrease the percentage of infected cells without causing any detectable toxic effects in mammalian host cells. The infective, i.e., trypomastigote form of T. cruzi pretreated with Pep5-cpp was unable to infect LLC-MK 2 monkey kidney cells. Also, Pep5-binding proteins were identified by mass spectrometry, including calmodulinubiquitin-associated protein, which is related to the virulence and parasitemia of T. cruzi. Taken together, these data suggest that Pep5 can be used as a novel alternative for the treatment of Chagas disease.

Intracellular Peptides in Cell Biology and Pharmacology

“…The infective form of T. cruzi , i.e., trypomastigotes, pre-treated with Pep5-cpp was unable to infect LLC-MK2 cells. These data suggest that Pep5 can be used as a novel alternative for the treatment of Chagas disease [78]. Altogether, these findings highlight the therapeutic potential of Pep5.…”

Peptidome: Chaos or Inevitability

“…It was shown that it participates in protection from cell death [ 170 ]. Another example is the peptide Pep5 derived from cyclin D2, which influences cell death in different types of tumor cells [ 171 , 172 ].…”