Chemosensitizer Effect of Violacein on Cisplatin-treated Bladder Cancer Cells  

作　　者：Diego Alem Lucía Canclini Susana Castro-Sowinski Wilner Martínez-López 

机构地区：[1]Genetics Department,Instituto de Investigaciones Biológicas Clemente Estable,Av.Italia 3318,11600,Montevideo,Uruguay [2]Biochemistry and Molecular Biology,Faculty of Sciences,Universidad de la República,Iguá4225,11400,Montevideo,Uruguay [3]Biodosimetry Service,Instituto de Investigaciones Biológicas Clemente Estable,Av.Italia 3318,11600,Montevideo,Uruguay [4]Molecular Microbiology,Instituto de Investigaciones Biológicas Clemente Estable,Av.Italia 3318,11600,Montevideo,Uruguay

出　　处：《Clinical Complementary Medicine and Pharmacology》2022年第2期50-58,共9页临床补充医学和药理学（英文）

基　　金：the National Agency for Re-search and Innovation(ANII-Uruguay).

摘　　要：Background:Bladder cancer is the tenth most common cancer worldwide.Considering its high prevalence(vulnerability to multiple recurrences and progression despite local therapy),which leads to a substantial health service burden,it becomes necessary to develop new strategies to increase the effectiveness of bladder tumor therapy.Natural compounds with antiproliferative effect on cancer cells could be a good choice for co-adjuvant chemotherapy.Microorganisms are one of the main sources for natural compounds.Pigments extracted from the cold-adapted microorganisms can contribute to the development of a broader range of applications in biotechnology.Violacein is a purple pigment commonly produced by many bacterial strains.We have previously shown that very low concentrations of violacein extracted from Janthinobacterium sp.produced an antiproliferative effect on HeLa cells.Objective:With the aim to determine if violacein has an antiproliferative activity on bladder cancer cells,as well as to test if it has synergistic effects on cisplatin treated cells in vitro,T24 and 253J cell lines(derived bladder cancer cells from carcinoma in situ and retroperitoneal metastasis,respectively)were exposed to different concentrations of violacein in the presence or absence of cisplatin.Methods:i)Resazurin assay and flow cytometry were performed in two bladder cancer-derived cell lines,namely T24 and 253J,to see if violacein affects cell viability and induce cell death.ii)To find out whether violacein sensitizes bladder cancer cells to cisplatin,the drug interaction among different doses of cisplatin and violacein was analyzed,as well their combination index was determined.iii)The effect of violacein to induce primary genetic damage was determined through the analysis of induced micronuclei frequency and𝛾H2AX foci,as well as performing the comet assay.Results:The half-maximal inhibitory concentration of violacein at 24 h for both cell lines were around 500 nM,and decreased below 400 nM in combination with 10μM of cisplatin,indica

关 键 词：Non-genotoxic CYTOTOXIC Natural product VIOLACEIN Cisplatin sensitization 

分 类 号：R73[医药卫生—肿瘤]