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