Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U...

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Bibliographic Details
Published in:Anticancer research 2017-09, Vol.37 (9), p.5225-5233
Main Authors: Bouhenna, Mustapha M, Orlikova, Barbora, Talhi, Oualid, Schram, Ben, Pinto, Diana C G A, Taibi, Nadia, Bachari, Khaldoun, Diederich, Marc, Silva, Artur M S, Mameri, Nabil
Format: Article
Language:English
Subjects:
Biological Assay
Caspase 3 - metabolism
Caspase 7 - metabolism
Cell Death - drug effects
Cell Proliferation - drug effects
Cell Survival - drug effects
Chromatography, High Pressure Liquid
Cyclohexanones - chemical synthesis
Cyclohexanones - chemistry
Cyclohexanones - pharmacology
Humans
K562 Cells
Leukemia - pathology
NF-kappa B - metabolism
Spironolactone - chemical synthesis
Spironolactone - chemistry
Spironolactone - pharmacology
Stereoisomerism
Tumor Necrosis Factor-alpha - pharmacology
U937 Cells
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Summary:NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) and spiro(6- methyllactone-cyclohexanone) down-regulated cancer cell viability and proliferation. Compound inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound and compound have potential as anti-cancer agents. In addition, compound exerted NF-kB inhibition activity in leukemia cancer cells.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.11946