Evaluation of crotoxin antitumoral activity in breast cancer: apoptose, autophagy and oxidative stress

• Grant number: 17/25532-6
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2018
• End date: May 31, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Maria Regina Torqueti
• Grantee: Maria Regina Torqueti
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Cleni Mara Marzocchi Machado

Abstract

Breast cancer is the neoplasia with the highest incidence rate among women in the world. Estrogens are indicated as the main risk factor for this pathology. SERMs (selective estrogen receptor modulators) and aromatase inhibitors (AI) and tyrosine kinase (TK) inhibitors are the established antineoplastic agents for breast cancer therapy because of their antiestrogenic properties. However, these drugs have many adverse effects, in addition to causing carcinomas resistant to treatment with them. Thus, the literature points to the antitumor action present in the poisons of several animals. In this study we will investigate the antitumor activity of Crotoxin, Crotalus durissus terrificus snake venom in apoptosis, autophagy and oxidative stress in cultures of estrogen-dependent (MCF-7) and overexpressing the aromatase gene (MCF -7aro), triple negative (MDA-MB-231), HER-2 overexpression independent estrogen (SKBR3) and resistant estrogen dependent resistance to AIs and SERM (LTEDaro), control of non-tumor mammary cell culture (MCF- 10A). Cellular cytotoxicity will be assessed by the MTT method; the induction of apoptosis by the expression of the pro-apoptotic genes BAX, CASP3, CASP8, CASP9, FAS, TP53 and anti-apoptotic BCL2 and BIRC4 by qRT-PCR; the expression of Beclina-1 and LC3 A / B autophagy indicating proteins by Western Blotting; and oxidative stress by the measurement of lipid peroxidation (malondialdehyde), oxidative DNA damage (8-OHdG) and reduced glutathione (GSH). For this, treatments with Crotoxin alone and in combination with the compounds used in the clinic for the treatment of mammary neoplasia will be used. Thus, will investigate the pathophysiology of breast cancer will be studied potential treatments for this disease. (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)

BEZERRA, PATRICIA H. A.; AMARAL, CRISTINA; ALMEIDA, CRISTINA F. F.; CORREIA-DA-SILVA, GEORGINA; TORQUETI, MARIA REGINA; TEIXEIRA, NATERCIA. In Vitro Effects of Combining Genistein with Aromatase Inhibitors: Concerns Regarding Its Consumption during Breast Cancer Treatment. Molecules, v. 28, n. 13, p. 14-pg., 2023-07-01. (17/25532-6)

ALMEIDA, CRISTINA FERREIRA; AMARAL, CRISTINA; AUGUSTO, V, TIAGO; CORREIA-DA-SILVA, GEORGINA; DE ANDRADE, CAMILA MARQUES; TORQUETI, MARIA REGINA; TEIXEIRA, NATERCIA. The anti-cancer potential of crotoxin in estrogen receptor-positive breast cancer: Its effects and mechanism of action. Toxicon, v. 200, p. 69-77, SEP 2021. (17/25532-6)