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Open AccessFeature PaperArticle

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

1
Division of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10000 Zagreb, Croatia
2
Division of Molecular Medicine, Laboratory for Protein Dynamics, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia
3
Division of Molecular Medicine, Laboratory for Advanced Genomics, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000 Zagreb, Croatia
4
University Hospital Merkur, Zajčeva 19, HR-10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Academic Editor: Riccardo Petrelli
Molecules 2020, 25(14), 3271; https://doi.org/10.3390/molecules25143271
Received: 23 June 2020 / Revised: 15 July 2020 / Accepted: 16 July 2020 / Published: 17 July 2020
(This article belongs to the Special Issue Bee Products: Recent Progress in Health Benefits Studies)
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. View Full-Text
Keywords: multimodal treatment; cisplatin; quercetin; bladder cancer cell lines; intracavitary drug administration; mice multimodal treatment; cisplatin; quercetin; bladder cancer cell lines; intracavitary drug administration; mice
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MDPI and ACS Style

Oršolić, N.; Odeh, D.; Jembrek, M.J.; Knežević, J.; Kučan, D. Interactions between Cisplatin and Quercetin at Physiological and Hyperthermic Conditions on Cancer Cells In Vitro and In Vivo. Molecules 2020, 25, 3271. https://doi.org/10.3390/molecules25143271

AMA Style

Oršolić N, Odeh D, Jembrek MJ, Knežević J, Kučan D. Interactions between Cisplatin and Quercetin at Physiological and Hyperthermic Conditions on Cancer Cells In Vitro and In Vivo. Molecules. 2020; 25(14):3271. https://doi.org/10.3390/molecules25143271

Chicago/Turabian Style

Oršolić, Nada; Odeh, Dyana; Jembrek, Maja J.; 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, no. 14: 3271. https://doi.org/10.3390/molecules25143271

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