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Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties


Ballazhi, Lulzime; Imeri, Faik; Jashari, Ahmed; Popovski, Emil; Stojković, Goran; Dimovski, Aleksandar J; Mikhova, Bozhana; Mladenovska, Kristina (2017). Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties. Acta Pharmaceutica, 67(1):35-52.

Abstract

This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski’s rule of five for good permeability (absorption) potential.

Abstract

This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski’s rule of five for good permeability (absorption) potential.

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Contributors:Andrea Huwiler and the Institute of Pharmacology at the University of Bern, Switzerland, for cooperation in cellular characterization of the synthesized coumarin derivatives
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2017
Deposited On:19 Jan 2018 16:32
Last Modified:30 May 2018 06:16
Publisher:De Gruyter
ISSN:1330-0075
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1515/acph-2017-0006

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