Assessment of potential anti-cancer stem cell activity of simvastatin, Copaifera oil-resin and novel nanoparticle s (graphene oxide modified with nickel and iron, and magnetite) in single or combined use, in human breast cancer derived cell lines

• Grant number: 16/04731-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2017
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: André Almeida Schenka
• Grantee: André Almeida Schenka
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Neoplastic or cancer stem cells (CSCs) are tumor cells which are able to mimic phenotypic and functional features of adult stem cells, such as self-renewal and multilineage potential. In addition, CSCs are resistent to the majority of xenobiotics (including classic antineoplastic drugs) since they present low proliferative index and express efflux pumps (such as Pgp and ABCG2). These characteristics allow them to play a fundamental role in the development/maintenance of malignant neoplasms, particularly in primary therapeutic failure and long-term recurrences. Most researchers in the field now believe that antineoplastic drugs with anti-CSC effects could be more efficient and less toxic, which makes these cells priority targets in pharmacological studies. Therefore, the present study aims to characterize the potential anti-CSC in vitro effects of 3 different substances, which have been shown to bear promising anti-CSC actions in preliminary tests performed in our laboratory. These include: simvastatin (an antidyslipidemic drug with partially characterized anti-neoplastic/anti-CSC actions, by our group and others), Copaifera reticulata Ducke oil (also known as Copaiba oil, a folk phytotherapic medicine commonly used for its anti-inflammatory, analgesic and antimycotic properties), and novel nanoparticles of graphene oxide (functionalized with iron and nickel) and of magnetite (functionalized with citric acid).These substances will be assessed either alone or in association with doxorubicin (a classic chemotherapeutic agent), using human cancer cell lines that represent the main molecular subtypes of mammary carcinoma (MCF-7, AU565, HCC1428, MDA-MB-231 and MACL-1, MGSO-3). Their effects on cell growth, cell cycle, apoptosis and CSC frequency will be assessed primarily in vitro, and then confirmed in vivo. We hope to contribute to the discovery of substances with anti-CSC associated anti-neoplastic activity from novel/poorly characterized molecules (Copaiba oil, graphene oxide and magnetite) and well-known drugs, currently used for other purposes (simvastatin). (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)

VIEIRA ROCHA, JOSE MARCOS; DE SOUZA, VALERIA BARBOSA; PANUNTO, PATRICIA COSTA; NICOLOSI, JACQUELINE SPACAGNA; DA SILVA, EMANUELI DO NASCIMENTO; CADORE, SOLANGE; LONDONO, OSCAR MOSCOSO; MURACA, DIEGO; TANCREDI, PABLO; DE BROT, MARINA; et al. In vitro and in vivo acute toxicity of a novel citrate-coated magnetite nanoparticle. PLoS One, v. 17, n. 11, p. 16-pg., 2022-11-17. (16/04731-8)

BRITTO-JUNIOR, JOSE; JACINTHO, FELIPE FERNANDES; CAMPOS, RAFAEL; ARAUJO PINHEIRO, DAVID HALEN; FIGUEIREDO MURARI, GUILHERME M.; DE SOUZA, VALERIA B.; SCHENKA, ANDRE A.; MONICA, FABIOLA Z.; MORENO, RONILSON AGNALDO; ANTUNES, EDSON; et al. The basal release of endothelium-derived catecholamines regulates the contractions of Chelonoidis carbonaria aorta caused by electrical-field stimulation. BIOLOGY OPEN, v. 10, n. 1, JAN 2021. (18/24971-9, 16/04731-8, 17/15175-1)

CAMPOS, RAFAEL; JACINTHO, FELIPE FERNANDES; BRITTO-JUNIOR, JOSE; MONICA, FABIOLA Z.; OLIVEIRA JUSTO, ALBERTO FERNANDO; PUPO, ANDRE SAMPAIO; MORENO, RONILSON AGNALDO; DE SOUZA, VALERIA BARBOSA; SCHENKA, ANDRE ALMEIDA; ANTUNES, EDSON; et al. Endothelium modulates electrical field stimulation-induced contractions of Chelonoidis carbonaria aortic rings. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 233, JUL 2020. (18/24971-9, 16/04731-8, 16/09539-8)