Evaluation of the antiproliferative potential of trichokonin VI and VIII peptaibols in MCF-7 and MDA-MB-231 breast Cancer cell lines

• Grant number: 21/09852-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2022
• End date: December 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Raquel Alves dos Santos
• Grantee: Natalia Nascimento Silveira
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil
• Associated research grant: 19/17721-9 - The role of Chemistry in holobiont adaptation, AP.TEM

Abstract

Natural products and their metabolites are of great importance in the development of new drugs. Trichoconine VI and VIII peptaibols (TK-VI and TK-VIII, respectively) are substances isolated from endolithic fungi of the genus Hypocrea sp., and, although antibacterial, antifungal, antiviral, antimalarial, and antiproliferative activity in tumoral cells, information on the biological activities of TK-VIII is not yet found in the literature. Considering the current scenario where there is a necessary and growing demand for antitumor agents, mainly due to the increase in cancer cases that results in the consequent increase in chemoresistance, as well as the need to obtain more information about the biological activity of these two peptaibols, some preliminary cytotoxicity experiments by the XTT assay on MCF-7 and MDA-MB-231 (chemoresistant) breast tumor cell lines. Preliminary results showed that after 24h of treatment were performed. TK-VI exhibits an IC50 of 7.9 µM for both cell lines, while for TK-VIII the IC50 is 5.4 and 10.02 µM for MDA-MB-231 and MCF-7 cell lines, respectively. In view of these results, this research project aims to investigate the antiproliferative effect of TK-VI and TK-VIII on MCF-7 and MDA-MB-231 cells. For this, experiments will be carried out to evaluate clonogenic survival, mitotic delay, cell death, and cell cycle, as well as molecular regulation after treatment with these substances. At the end of the research, we hope to answer the following question: do TK-VI and TK-VIII have an antiproliferative effect and induce cell death in the tumoral cell lines tested here? Is the DNA damage signaling pathway modulated by these substances? Which of the two cell lines is more sensitive to the treatment with these substances?(AU)