Mechanism of action of the bioactive compound Artepillin C in membrane biomimetic systems and cytoplasmic membrane of tumor cells

• Grant number: 16/09633-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): September 01, 2016
• Effective date (End): September 30, 2020
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Carlos José Leopoldo Constantino
• Grantee: Wallance Moreira Pazin
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Associated research grant: 13/14262-7 - Nanostructured films from biologically-relevant materials, AP.TEM
• Associated scholarship(s): 17/23426-4 - Insights on the interaction of Artepillin C with tumor cell membranes: an advanced fluorescence microscopy study, BE.EP.PD

Abstract

Green propolis is a mixture of bees wax and resinous compounds processed by the species Apis mellifera, with a broad spectrum of pharmacological properties. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid), is the major identified compound of green propolis, constituted by two prenylated groups bound to a phenyl group. The antitumor effects of this molecule have been the focus of several studies, but so far there is no evidence for its interaction with amphiphilic aggregates that mimic membranes of tumor cells, which may be the initial step essential to elicit the biological action of Artepillin C, mainly due its amphiphilic propertie, probably promoting dynamic and structural alterations in the membranes. These features motivate us to investigate the mechanism of action of the compound Artepillin C in membranes of tumor cells and their models, investigating particularities as lipid composition, lateral organization and the influence of microdomains in their structures, as such as the concentration of the bioactive compound for the action and the influence of pH and ionic strength in the system. The presented project is part of the thematic "Nanostructured films from biologically-relevant materials", FAPESP process 2013/14262-7, will be developed by means of methodologies based on fluorescence microscopy, using giant unilamellar vesicles (GUVs), Langmuir monolayers and Langmuir-Blodgett (LB) films as membrane biomimetic systems.

Scientific publications

(16)

(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)

CALORI, ITALO RODRIGO; PAZIN, WALLANCE MOREIRA; BRUNALDI, KELLEN; PELLOSI, DIOGO SILVA; CAETANO, WILKER; TEDESCO, ANTONIO CLAUDIO; HIOKA, NOBORU. Laurdan as fluorescent probe to determinate the critical micelle temperature of polymers from Pluronic (R)-coated fluid phase liposomes. JOURNAL OF MOLECULAR LIQUIDS, v. 294, NOV 15 2020. (16/09633-4)

PAZIN, WALLANCE MOREIRA; MARQUES RUIZ, GILIA CRISTINE; DOS SANTOS, MARCELO JOSE; BENITES AOKI, PEDRO HENRIQUE; ITO, AMANDO SIUITI; LEOPOLDO CONSTANTINO, CARLOS JOSE. The protective effect of Artepillin C against lipid oxidation on model membranes. JOURNAL OF MOLECULAR LIQUIDS, v. 324, FEB 15 2021. (16/09633-4, 18/22214-6, 18/16713-0)

PAZIN, WALLANCE MOREIRA; MARQUES RUIZ, GILIA CRISTINE; DE OLIVEIRA, JR., OSVALDO NOVAIS; LEOPOLDO CONSTANTINO, CARLOS JOSE. Interaction of Artepillin C with model membranes: Effects of pH and ionic strength. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1861, n. 2, p. 410-417, FEB 1 2019. (13/14262-7, 16/09633-4)

MARQUES RUIZ, GILIA CRISTINE; PAZIN, WALLANCE MOREIRA; DO CARMO MORATO, LUIS FERNANDO; OLIVEIRA JR, OSVALDO N.; LEOPOLDO CONSTANTINO, CARLOS JOSE. Correlating mono- and bilayers of lipids to investigate the pronounced effects of steroid hormone 17 alpha-ethynylestradiol on membrane models of DPPC/cholesterol. JOURNAL OF MOLECULAR LIQUIDS, v. 311, AUG 1 2020. (13/14262-7, 16/09633-4)

CAMURI, ISAMARA JULIA; COSTA, ADRIANO BATISTA; ITO, AMANDO SIUITI; PAZIN, WALLANCE MOREIRA. Optical absorption and fluorescence spectroscopy studies of Artepillin C, the major component of green propolis. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, v. 198, p. 71-77, JUN 5 2018. (16/09633-4)

PAZIN, WALLANCE M.; DOS SANTOS, SUIKINAI N.; QUEIROZ, SONIA C. N.; BAGATOLLI, LUIS A.; SOARES, ADEMILSON E. E.; DE MELO, ITAMAR S.; ITO, AMANDO S.. Bioactivity and action mechanism of green propolis against Pythium aphanidermatum. Anais da Academia Brasileira de Ciências, v. 91, n. 2, 2019. (16/09633-4)

DE CAMPOS, ISABELE AP. S.; DOS SANTOS, EDJANE R.; SELLANI, TARCISO ALMEIDA; HERBOZO, CAROLINA C. A.; RODRIGUES, ELAINE G.; ROVEDA, ANTONIO C.; PAZIN, WALLANCE M.; ITO, AMANDO S.; SANTANA, VINICIUS T.; NASCIMENTO, OTACIRO R.; et al. Influence of the Medium on the Photochemical and Photophysical Properties of [Ru(phen)(2)(pPDIp)](2+). CHEMPHOTOCHEM, v. 2, n. 8, p. 757-764, AUG 2018. (17/00839-1, 16/09633-4)

PAZIN, W. M.; VILANOVA, N.; VOETS, I. K.; SOARES, A. E. E.; ITO, A. S.. Effects of artepillin C on model membranes displaying liquid immiscibility. Brazilian Journal of Medical and Biological Research, v. 52, n. 3, 2019. (16/09633-4)

PAZIN, W. M.; ITO, A. S.; CONSTANTINO, C. J. L.. Influence of pH on the therapeutic effects of Artepillin C: enhancing its use as an anticancer drug. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, v. 46, p. 1-pg., 2017-07-01. (16/09633-4)

MARQUES RUIZ, GILIA CRISTINE; DO CARMO MORATO, LUIS FERNANDO; PAZIN, WALLANCE MOREIRA; MILANO, FRANCESCO; LEOPOLDO CONSTANTINO, CARLOS JOSE; VALLI, LUDOVICO; GIOTTA, LIVIA. Chemical and morphological effects of the contraceptive hormone 17 alpha-ethynylestradiol on fluid lipid membranes. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 204, AUG 2021. (16/09633-4)

PAZIN, WALLANCE M.; FURINI, LEONARDO N.; SOLOVYEVA, VITA; LEMMA, TIBEBE; RUBIRA, RAFAEL J. G.; JORGENSEN, BJARKE; CONSTANTINO, CARLOS J. L.; BREWER, JONATHAN R.. Vibrational Spectroscopic Characterization and Coherent Anti-Stokes Raman Spectroscopy (CARS) Imaging of Artepillin C. Applied Spectroscopy, v. 74, n. 7, APR 2020. (16/09633-4, 17/23426-4)

PAZIN, WALLANCE MOREIRA; MONACO, LUCIANA DA MATA; EGEA SOARES, ADEMILSON ESPENCER; MIGUEL, FELIPE GALETI; BERRETTA, ANDRESA APARECIDA; ITO, AMANDO SIUITI. Antioxidant activities of three stingless bee propolis and green propolis types. JOURNAL OF APICULTURAL RESEARCH, v. 56, n. 1, p. 40-49, 2017. (16/09633-4)

FERNANDES, JOSE DIEGO; PAZIN, WALLANCE MOREIRA; AROCA, RICARDO FLAVIO; MACEDO JUNIOR, WAGNER DIAS; TEIXEIRA, SILVIO RAINHO; LEOPOLDO CONSTANTINO, CARLOS JOSE. Photoluminescent properties in perylene PVD films: Influence of molecular aggregates and supramolecular arrangement. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, v. 211, p. 221-226, MAR 15 2019. (13/14262-7, 16/09633-4)

KOBAL, MIRELLA B.; PAZIN, WALLANCE M.; BISTAFFA, MARIA J.; CONSTANTINO, CARLOS J. L.; TOLEDO, KARINA A.; AOKI, PEDRO H. B.. Correlating Artepillin C cytotoxic activity on HEp-2 cells with bioinspired systems of plasma membranes. Materials Science & Engineering C-Materials for Biological Applications, v. 112, JUL 2020. (18/02392-7, 16/09633-4)

FERNANDES, JOSE DIEGO; PAZIN, WALLANCE MOREIRA; MACEDO, WAGNER COSTA; TEIXEIRA, SILVIO RAINHO; LIMA, SERGIO ANTONIO MARQUES; BATAGIN-NETO, AUGUSTO; CONSTANTINO, CARLOS JOSE LEOPOLDO. Perylene derivative films: Emission from higher singlet excited state. Journal of Luminescence, v. 226, OCT 2020. (13/14262-7, 16/09633-4)

CALORI, ITALO RODRIGO; PAZIN, WALLANCE MOREIRA; BRUNALDI, KELLEN; PELLOSI, DIOGO SILVA; CAETANO, WILKER; TEDESCO, ANTONIO CLAUDIO; HIOKA, NOBORU. Laurdan as fluorescent probe to determinate the critical micelle temperature of polymers from Pluronic®-coated fluid phase liposomes. JOURNAL OF MOLECULAR LIQUIDS, v. 294, p. 9-pg., 2019-11-15. (16/09633-4)