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

Grant number: 17/25532-6
Support type:Regular Research Grants
Duration: June 01, 2018 - May 31, 2021
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Maria Regina Torqueti
Grantee:Maria Regina Torqueti
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. 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)