Abstract
Quercetin (QU), a hyperthermic sensitizer, when combined with cisplatin (CP) affects tumor growth. To determine the effects of QU and CP and their interactions, multimodal treatment in vitro and in vivo models under physiological and hyperthermic conditions was performed. In vitro, different sensitivity of T24 and UMUC human bladder cancer cells was observed after short-term exposure to QU (2 h) and CP (1 h). Effects of both compounds were investigated at low and high micromolar concentrations (1 and 50 µM, respectively) under both thermal conditions. QU acted in additive or synergistic manner in combination with CP between physiological condition and hyperthermia. As determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, short-term application of QU and CP reduced cell viability. Clonal assay also indicated that combined treatment with QU and CP is lethal to bladder cancer cells in both conditions. In vivo, CP (5 or 10 mg kg−1) and QU (50 mg kg−1) acted synergistically with hyperthermia (43 °C) and inhibited tumor growth, activated immune effectors and increased mice survival. Our results demonstrate that combined treatment with CP and QU may increase death of tumor cells in physiological and hyperthermic conditions which could be clinically relevant in locoregional chemotherapy.
Highlights
Bladder cancer (BC) is a significant problem worldwide and one of the leading cause of death.American Cancer Society estimated 81,400 new cases of BC and approximately 17,980 deaths in 2020 [1]
Numerous risk factors may be involved in the development of BC, including smoking, work-related exposure to aromatic amines and polyurethane products, hereditary genetic background, nutritional factors, certain medical conditions, long-term treatment with chemotherapy agents, such as cyclophosphamide or immunosuppressive drugs like glucocorticoids, age, sex, ethnicity, race, and socio-economic status
There were no significant differences in the percentage of cell viability (MTT test) under physiological and hyperthermic conditions for T24 cells treated with QU: percentage of cell viability for Q1 was
Summary
Bladder cancer (BC) is a significant problem worldwide and one of the leading cause of death. American Cancer Society estimated 81,400 new cases of BC and approximately 17,980 deaths in 2020 [1]. From the economic point of view, BC is the most expensive cancer to treat as it frequently requires diagnostic procedures such as cystourethroscopy, urine cytology, and radiological imaging [2]. Numerous risk factors may be involved in the development of BC, including smoking, work-related exposure to aromatic amines and polyurethane products, hereditary genetic background, nutritional factors, certain medical conditions, long-term treatment with chemotherapy agents, such as cyclophosphamide or immunosuppressive drugs like glucocorticoids, age, sex, ethnicity, race, and socio-economic status. The highest rates are reported in European countries such as Denmark, UK, Belgium, and Italy, whereas the lowest rates are observed
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