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Antiproliferative and toxicogenetic effects of simultaneous treatment with alila isothiocyanate and cisplatin in bladder carcinoma cells

Grant number: 19/15352-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2019
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Principal Investigator:Daisy Maria Favero Salvadori
Grantee:Phillipe Franklin Coelho Magalhães
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Worldwide, bladder cancer is the seventh most common neoplasia in men and the seventeenth in women, and the urothelial cell carcinoma (UCC) is responsible for approximately 90% of these malignant tumors. The most used and successful chemotherapies for UCC include combinations of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), or combination of gemcitabine and cisplatin. Commonly, these protocols induce changes in DNA and in cell cycle, with high toxic activity to the body. Today, several studies have been carried out in attempt to identify natural antiproliferative compounds with lower toxicity to the non-neoplastic cells. Based on previous data from our laboratory that showed the antiproliferative activity of allyl isothiocyanate (AITC), the present study aims to investigate the cytotoxic and toxicogenic effect of the combined treatment with AITC and cisplatin (CIS) in two lines of bladder carcinoma: RT4 (with wild-type TP53 gene) and UMUC3 (with mutated TP53). Cytotoxicity (MTS test), clonogenic survival, DNA damage (comet assay) and chromosomal changes (micronucleus test) will be analyzed. It is expected that the results might contribute to identify effective natural compounds as adjuvants in therapy for urothelial carcinoma, but with lower toxic effects to the organism.