Study of the cytotoxicity, genotoxicity, cell cycle monitoring, induction of apoptosis, and gene expression of Rubus rosaefolius leaves and stems extracts in human cultured cells.

• Grant number: 17/24149-4
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2018
• End date: April 30, 2020
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Edson Luis Maistro
• Grantee: Edson Luis Maistro
• Host Institution: Faculdade de Filosofia e Ciências (FFC). Universidade Estadual Paulista (UNESP). Campus de Marília. Marília , SP, Brazil
• Associated researchers: Mário Sérgio Mantovani

Abstract

The Rubus rosaefolius plant recently have been some of its therapeutic properties confirmed by scientific analysis, among them the analgesic, antimicrobial, antihypertensive, antioxidant, antiproliferative effects in tumor cells, diuretic, gastroprotective and antidepressant. Such confirmation makes this plant of great interest to the pharmaceutical industry. However, before the commercial exploitation of R. rosaefolius as a herbal remedy, it is necessary to carry out tests evaluating the biosafety of the use of this plant by humans, ascertaining if it is free of cellular and genetic toxicity. In view of the above context, this research aims to identify the cytotoxic and genotoxic potential in HepG2/C3A and human leukocytes; and effects on the cell cycle progression, action on the apoptosis induction, of leaf and stem extracts of R. rosaefolius, in HepG2/C3A cells (Human hepatoma). In addition, this study will to investigate the possible mechanism of action of the both extracts, through the analysis of the gene expression of some of the main genes of these biochemical pathways. For this, the first stage of the work will seek to observe effects of cytotoxicity of the extract, by MTT test, trypan blue staining, genotoxicity by comet and micronucleus assays, and on cell cycle progression and induction of apoptosis, by flow cytometry. The second stage of the research will include, through real-time qRT-PCR analysis, the investigation of the relative expression of genes involved in the above-mentioned processes that have had some interesting biological effect after exposure to the extracts. The development of this project will allow the formation of qualified human resources at doctoral level and scientific initiation, as well as the implantation in the laboratory, the molecular techniques involving the analysis of gene expression (qRT-PCR), and flow cytometry, which have the potential to elucidate the Mechanisms of action of the phytotherapeutics (and its constituents) routinely investigated in the Toxicological Genetics Laboratory. (AU)

Scientific publications

(9)

(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)

MAISTRO, EDSON LUIS; TERRAZZAS, PETERSON MENEZES; HELENA FRANKLAND SAWAYA, ALEXANDRA CHRISTINIE; PIRES ROSA, PAULO CESAR; PERAZZO, FABIO FERREIRA; DE MASCARENHAS GAIVAO, ISABEL O'NEILL. In vivo toxicogenic potential of Salix alba (Salicaceae) bark extract. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, OCT 2021. (17/24149-4)

MARTINS CASTANHA, ANA PAULA; ALMEIDA-TERASSI, LAIZA MOURA; GUARDADO-YORDI, ESTELA; JOAO MATOS, MARIA; MAISTRO, EDSON LUIS. Cytogenotoxicity assessment of 3-(3,4-dihydroxyphenyl)-7,8-dihydroxycoumarin on HepG2/C3A cells and leukocytes. JOURNAL OF APPLIED TOXICOLOGY, v. 43, n. 2, p. 12-pg., 2022-09-02. (17/24149-4)

DOS SANTOS SILVA, EDVANNIA; MATOS, MARIA JOAO; MAISTRO, EDSON LUIS. Evaluation of in vitro cytotoxic and genotoxic effects of the 3-(3,4-dihydroxyphenyl)-8-hydroxycoumarin. JOURNAL OF APPLIED TOXICOLOGY, v. 43, n. 10, p. 11-pg., 2023-05-08. (17/24149-4)

SILVA, BRIAN OGUSHI; ORLANDO, JULIANA BOTINHON; PIRES, CAMILA LEHNHARDT; HIRUMA-LIMA, CLELIA AKIKO; DE MASCARENHAS GAIVAO, ISABEL; PERAZZO, FABIO FERREIRA; MAISTRO, EDSON LUIS. Genotoxicity induced by nerol, an essential oil present in citric plants using human peripheral blood mononuclear cells (PBMC) and HepG2/C3A cells as a model. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 84, n. 12, MAR 2021. (17/24149-4)

PIRES, CAMILA LEHNHARDT; ZANETTI, THALITA ALVES; MANTOVANI, MARIO SERGIO; GAIVAO, ISABEL O'NEILL DE MASCARENHAS; PERAZZO, FABIO FERREIRA; ROSA, PAULO CESAR PIRES; MAISTRO, EDSON LUIS. Pracaxi oil affects xenobiotic metabolisms, cellular proliferation, and oxidative stress without cytotogenotoxic effects in HepG2/C3A cells. TOXICOLOGY IN VITRO, v. 83, p. 9-pg., 2022-06-03. (17/24149-4)

DE QUADROS, ANA PAULA OLIVEIRA; OSHIIWA, BRUNA; PETREANU, MARCEL; NIERO, RIVALDO; ROSA, PAULO CESAR PIRES; SAWAYA, ALEXANDRA CHRISTINE HELENA FRANKLAND; MANTOVANI, MARIO SERGIO; GAIVAO, ISABEL O'NEILL DE MASCARENHAS; MAISTRO, EDSON LUIS. Rubus rosifolius (Rosaceae) stem extract induces cell injury and apoptosis in human hepatoma cell line. TOXICOLOGY IN VITRO, v. 86, p. 10-pg., 2023-02-01. (17/24149-4)

MAISTRO, E. L.; QUADROS, A. P.; ALMEIDA, L.; BARALDI, I.; NIERO, R.; PETREANU, M.; MANTOVANI, M.. Screening of the cytotoxic, genotoxic, apoptotic and cell cycle effects of Rubus rosaefolius (Rosaceae) leaf extract on human HepG2/C3A cells.. Toxicology Letters, v. 314, p. 2-pg., 2019-10-15. (17/24149-4)

QUADROS, ANA PAULA OLIVEIRA DE; ALMEIDA, LAIZA MOURA; PETREANU, MARCEL; NIERO, RIVALDO; ROSA, PAULO CESAR PIRES; SAWAYA, ALEXANDRA CHRISTINIE HELENA FRANKLAND; MANTOVANI, MARIO SERGIO; GAIVAO, ISABEL O'NEILL DE MASCARENHAS; MAISTRO, EDSON LUIS. Risk assessment via genotoxicity, metabolism, apoptosis, and cell growth effects in a HepG2/C3A cell line upon treatment withRubus rosifolius(Rosaceae) leaves extract. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 83, n. 13-14, p. 495-508, JUL 17 2020. (17/24149-4)

DE QUADROS, ANA PAULA OLIVEIRA; BARALDI, ISABEL BRAGANCA; PETREANU, MARCEL; NIERO, RIVALDO; MANTOVANI, MARIO SERGIO; GAIVAO, ISABEL O'NEILL DE MASCARENHAS; MAISTRO, EDSON LUIS. Cytogenotoxic evaluations of leaves and stems extracts of Rubus rosifolius in primary metabolically noncompetent cells. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. N/A, p. 11-pg., 2023-04-22. (17/24149-4)