Plant-derived compounds that target histone acetyltransferases inhibit Trypanosoma cruzi proliferation and viability and affect parasite ultrastructure

Abstract

Trypanosoma cruzi, the causative agent of Chagas disease, exhibits a chromatin structure and organization similar to that of other eukaryotes, undergoing certain epigenetic modifications, such as histone acetylation and deacetylation. Histone acetyltransferase inhibitors have been frequently applied as therapy agents against tumor cells, but their effects on protozoa have not yet been adequately explored. In this study, the effects of three acetyltransferase inhibitors, curcumin, triptolide and anacardic acid, were investigated on T. cruzi. Curcumin was able to inhibit epimastigote and amastigote proliferation and was the most effective compound. Triptolide also impaired T. cruzi proliferation and, along with curcumin, promoted the unpacking of nuclear heterochromatin and nucleolus disorganization. Anacardic acid did not alter parasite growth or viability, but caused ultrastructural changes, such as mitochondrial swelling and cristae enlargement. None of these compounds affected the microtubule cytoskeleton. These findings indicate that histone acetyltransferase inhibitors, especially curcumin, display the potential to be applied in chemotherapeutic studies against T. cruzi. Our results reinforce the necessity of developing new compounds that can be used successfully in therapy against neglected diseases.

Keywords: Acetyltransferase inhibitors; Chromatin condensation; Epigenetic modification; Histone; Trypanosoma cruzi; Ultrastructure.