Risk assessment via genotoxicity, metabolism, apoptosis, and cell growth effects in a HepG2/C3A cell line upon treatment withRubus rosifolius(Rosaceae) leaves extract

Author(s)

Quadros, Ana Paula Oliveira De ^{[1, 2]} ; Almeida, Laiza Moura ^{[3, 4]} ; Petreanu, Marcel ^[5] ; Niero, Rivaldo ^[5] ; Rosa, Paulo Cesar Pires ^[6] ; Sawaya, Alexandra Christinie Helena Frankland ^[6] ; Mantovani, Mario Sergio ^[7] ; Gaivao, Isabel O'Neill De Mascarenhas ^{[8, 9]} ; Maistro, Edson Luis ^{[3, 1, 4]}

Affiliation

^[1] Sao Paulo State Univ, UNESP, Biosci Inst, Postgrad Program Gen & Appl Biol, Botucatu, SP - Brazil

^[2] UNIRP, Ctr Univ Rio Preto, Dept Biomed, Sao Jose Do Rio Preto, SP - Brazil

^[3] Marilia Med Sch, Marilia, SP - Brazil

^[4] Sao Paulo State Univ, UNESP, Fac Philosophy & Sci Marilia, Speech & Hearing Therapy Dept, BR-17525900 Marilia, SP - Brazil

^[5] Vale Itajai Univ UNIVALI, Dept Biol Sci, Itajai, SC - Brazil

^[6] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP - Brazil

^[7] Univ Estadual Londrina, Dept Gen Biol, Londrina, PR - Brazil

^[8] Univ Tras Os Montes & Alto Douro, CECAV, Vila Real - Portugal

^[9] Univ Tras Os Montes & Alto Douro, Dept Genet & Biotechnol, Vila Real - Portugal

• Document type: Journal article
• Source: JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES; v. 83, n. 13-14, p. 495-508, JUL 17 2020.
• Web of Science Citations: 1

Abstract

Rubus rosifolius Sm. (Rosaceae) is a plant traditionally used in Brazil and some other countries to treat diarrhea, stomach diseases, and as an analgesic, antimicrobial, antihypertensive, and as well as other pharmacological properties. The aim of this study was to examine cytotoxic and genotoxic effects ofR. rosifoliusleaves extract on HepG2/C3A cells and correlate these findings with the expression of mRNA to underlying mechanisms of action. At concentrations between 0.01 and 100 mu g/ml, cytotoxic effects were not detected by the MTT assay. This was confirmed by mRNA induction of theCYP3A4gene (by RT-qPCR assay). However, genotoxic effects occurred at treatments from 1 mu g/ml extract (comet and micronucleus test). An increase in the number of cells in S phase was observed at 100 mu g/ml, and an elevation in apoptotic cell number was found for all tested concentrations (10, 20, or 100 mu g/ml) (cell cycle and apoptosis analysis by flow cytometry). The genotoxicity induced by the extract was the main cause of the rise in the number of cells undergoing apoptosis, as indicated by rise in mRNA ofCASP7gene, and elevation of cells in the S phase of the cell cycle at the higher tested concentrations, as an attempt to repair genetic damage that occurred. These observations suggest that, despite its pharmacological potential, the use ofR. rosifoliusleaves extract may pose a risk to the integrity of the genetic material of human cells. (AU)

• FAPESP's process: 17/24149-4 - 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.
• Grantee: Edson Luis Maistro
• Support Opportunities: Regular Research Grants