Interactions between Cisplatin and Quercetin at Physiological and Hyperthermic Conditions on Cancer Cells In Vitro and In Vivo

Oršolić, Nada; Odeh, Dyana; Jazvinšćak Jembrek, Maja; Knežević, Jelena; Kučan, Darko (2020) Interactions between Cisplatin and Quercetin at Physiological and Hyperthermic Conditions on Cancer Cells In Vitro and In Vivo. Molecules, 25 (14). ISSN 1420-3049

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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) and QU (50 mg/kg) 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.

Item Type:	Article
Uncontrolled Keywords:	multimodal treatment ; cisplatin ; quercetin ; bladder cancer cell lines ; intracavitary drug administration ; mice
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division of Molecular Medicine
Depositing User:	Jelena Knežević
Date Deposited:	07 Jan 2021 14:12
URI:	http://fulir.irb.hr/id/eprint/6158
DOI:	10.3390/molecules25143271

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