Studies of cellular and molecular mechanisms of tumor cell death induced by antimicrobial peptides

• Grant number: 16/18990-5
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2017
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Edgar Julian Paredes-Gamero
• Grantee: Edgar Julian Paredes-Gamero
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Antonio de Miranda ; Edwin Alexander Yates ; Jaime Shinsuke Ide ; Marcelo Andrade de Lima ; Tiago Rodrigues ; Wagner Alves de Souza Júdice

Abstract

Antimicrobial peptides (AMPs) are defensive molecules found in different organisms. Besides its antimicrobial activity, different studies have shown other potential activities of these kinds of peptides, including antitumor and immunomodulatory effect. Our group described the cytotoxic activity of some b-hairpin AMPs, such as polyphemusin, tachyplesin, protegrin and gomesin. Their mechanisms of cell death were triggered by AMPs in erythroleukemic myeloid line K562 and other cell types such as melanoma, neuroblastoma and Chinese hamster ovary cells. Furthermore, we described that the AMPs cited above produced direct disruption of the plasma membrane at high concentrations (>20 µM), whereas intermediate concentrations induced different kinds of cell death. These kinds of induced cell death seem to be characteristic of the AMP used, although they present high homology of sequences and structures. In this work, we intend to continue our studies on antitumor activity of ²-hairpin AMPs (protegrin, tachyplesin, polyphemusin and gomesin), by focusing the following aspects: 1) To compare the cytotoxic effects on normal and tumor leukemic cells to identify the possible mechanisms that confer resistance to AMPs; 2) To evaluate the mechanisms of cell death of adenocarcinoma tumor cells HELA induced by AMP, and to investigate their internalization into the cells by using image (confocal mycroscopy e photothermal heterodyne imaging) and mass spectrometry. The mechanisms of cell death will be also evaluated by multiparametric methodologies, such as, PCRarray and flow cytometry. The involvement of glycosaminoglycans in the internalization of AMPs into cells will also be assessed; 3) To determine if the AMPs also acts in organelles, such as, mitochondria and endoplasmic reticulum. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VITAL, WAGNER D.; TORQUATO, HERON F. V.; PASSOS JESUS, LARISSA DE OLIVEIRA; DE SOUZA JUDICE, WAGNER ALVES; DA SILVA, MARIA FATIMA DAS G. F.; RODRIGUES, TIAGO; JUSTO, GISELLE ZENKER; VEIGA, THIAGO A. M.; PAREDES-GAMERO, EDGAR J.. 4-Deoxyraputindole C induces cell death and cell cycle arrest in tumor cell lines. Journal of Cellular Biochemistry, v. 120, n. 6, p. 9608-9623, JUN 2019. (16/18990-5, 18/04095-0, 16/25112-4)

DE NOVAIS, LEICE M. R.; FERREIRA, LUIZ F.; DE SOUSA, JR., PAULOT.; RIBEIRO, TEREZA A. N.; JACINTO, MARCOS J.; DOS SANTOS, CARLOS H. C.; DE CARVALHO, MARIO G.; TORQUATO, HERON F. V.; PAREDES-GAMERO, EDGAR J.; SILVA, VIRGINIA C. P.. Eglerisine, a Novel Sesquiterpenoid Tropolone from Dulacia egleri with Antiproliferative Effect against an Acute Myeloid Leukemia Lineage. Planta Medica, v. 86, n. 1, p. 55-60, JAN 2020. (16/18990-5)

TORQUATO, V, HERON F.; RODRIGUES JUNIOR, MANOEL TRINDADE; LIMA, CAUE SANTOS; DE ARAUJO JUNIOR, ROBERTO THEODORO; TALHATI, FERNANDA; DIAS, DHEBORA ALBUQUERQUE; JUSTO, GISELLE ZENKER; FERREIRA, ALICE TEIXEIRA; PILLI, RONALDO ALOISE; PAREDES-GAMERO, EDGAR J.. A canthin-6-one derivative induces cell death by apoptosis/necroptosis-like with DNA damage in acute myeloid cells. BIOMEDICINE & PHARMACOTHERAPY, v. 145, JAN 2022. (16/18990-5)