Toxigenomic evaluation of diallyl disulfide effects and its association with chemothepeutic 5-fluorouracil in cellular lineages of human colorectal adenocarcinoma

• Grant number: 22/13151-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2023
• End date: August 31, 2024
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Lusânia Maria Greggi Antunes
• Grantee: Estéfani Maria Treviso
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Colorectal cancer (CRC) is one of the most common cancers and it represents about 10% of incidence and 9.4% of global cancer mortality, according to data released in 2020. The progress in treatment of CRC with chemotherapeutics drugs in the last 70 years was very limited, and the therapy with 5-fluorouracil still represents the bases of chemotherapy in many clinical protocols, including the Brazilian Public Health System (Sistema Unico de Saude [SUS]-Brazil). The search for new strategies to enhance de therapeutic efficacy of 5-fluorouracil, with reduced adverse effects, includes association between the chemotherapy and nutraceuticals, that inhibit the proliferation process of tumor cells. These nutraceuticals target various cell signaling pathways and can increase antitumoral activity through synergic action or reducing the adverse effects. Among garlic-derived nutraceuticals, diallyl disulfide (DADS) could be used to sensitize tumors that present resistance to chemotherapeutic agents. There is no data in the literature about the effects on the association between 5-fluorouracil and DADS in cellular lineages of human colorectal adenocarcinoma. The hypothesis of this study is that the associations between the nutraceutical DADS and the chemotherapeutic drug 5-fluorouracil will present synergistic results on apoptosis, genotoxicity and inhibition of cellular proliferation and migration, besides epigenetic modulation in human colorectal adenocarcinoma in vitro.Colorectal cancer (CRC) is one of the most common cancers and it represents about 10% of incidence and 9.4% of global cancer mortality, according to data released in 2020. The progress in treatment of CRC with chemotherapeutics drugs in the last 70 years was very limited, and the therapy with 5-fluorouracil still represents the bases of chemotherapy in many clinical protocols, including the Brazilian Public Health System (Sistema Unico de Saude [SUS]-Brazil). The search for new strategies to enhance de therapeutic efficacy of 5-fluorouracil, with reduced adverse effects, includes association between the chemotherapy and nutraceuticals, that inhibit the proliferation process of tumor cells. These nutraceuticals target various cell signaling pathways and can increase antitumoral activity through synergic action or reducing the adverse effects. Among garlic-derived nutraceuticals, diallyl disulfide (DADS) could be used to sensitize tumors that present resistance to chemotherapeutic agents. There is no data in the literature about the effects on the association between 5-fluorouracil and DADS in cellular lineages of human colorectal adenocarcinoma. The hypothesis of this study is that the associations between the nutraceutical DADS and the chemotherapeutic drug 5-fluorouracil will present synergistic results on apoptosis, genotoxicity and inhibition of cellular proliferation and migration, besides epigenetic modulation in human colorectal adenocarcinoma in vitro.