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Quinoline based mono- and bis-(thio) carbohydrazones: synthesis, anticancer activity in 2D and 3D cancer and cancer stem cell models

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2016
1893.pdf (3.424Mb)
Authors
Božić, Aleksandra R.
Marinković, Aleksandar D.
Bjelogrlić, Snežana K.
Todorović, Tamara
Cvijetić, Ilija
Novaković, Irena
Muller, Christian D.
Filipovic, Nenad R.
Article (Published version)
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Abstract
A comparative study of antitumor activity of mono- and bis-quinoline based (thio) carbohydrazones was investigated by a series of tests on two human malignant cell lines: acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma cancer stem cells (AsPC-1). Thiocarbohydrazones (TCHs) revealed superior pro-apoptotic activity over carbohydrazones (CHs) on both tested cell phenotypes, also displaying multi-target profile activities. Programmed cell death triggered by TCHs was partially caspase-dependent, mainly caspase-8 related. Activity against cancer stem cells (CSCs) was evaluated on 2D monolayers and 3D spheroidal models, where two out of three tested bis-TCHs successfully stimulated apoptosis accompanied by a reduction in size of treated spheres. Additionally, all bis-TCHs induced significant decrease in percentage of CD44-expressing AsPC-1 cells that indicate on their ability to induce reprogramming of CSC phenotype. Current results highly support further assessment of bis-TCHs... in order to specify their specific targets in cancer cells and particularly in the CSCs subpopulation.

Source:
RSC Advances, 2016, 6, 106, 104763-104781
Publisher:
  • Royal Soc Chemistry, Cambridge
Projects:
  • Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)
  • Study of the Synthesis, Structure and Activity of Natural and Synthetic Organic Compounds (RS-172013)
  • COST Action CM1106 StemChem - "Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells"

DOI: 10.1039/c6ra23940d

ISSN: 2046-2069

WoS: 000388111900107

Scopus: 2-s2.0-84994477669
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URI
http://cer.ihtm.bg.ac.rs/handle/123456789/1895
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IHTM

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