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

Abstract

BACKGROUND/AIM:

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).

MATERIALS AND METHODS:

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.

RESULTS:

Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines.

CONCLUSION:

Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells.

• Authors: Mustapha M Bouhenna, Barbora Orlikova, Oualid Talhi, Ben Schram, Diana C G A Pinto, Nadia Taibi, Khaldoun Bachari, Marc Diederich, Artur M S Silva, Nabil Mameri
• Journal: Anticancer research (Anticancer Res) Vol. 37 Issue 9 Pg. 5225-5233 (09 2017) ISSN: 1791-7530 [Electronic] Greece
• PMID: 28870958 (Publication Type: Journal Article)
• Copyright: Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Cyclohexanones
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Spironolactone
• cyclohexanone
• Caspase 3
• Caspase 7

Topics

• 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, chemistry, pharmacology)
• Humans
• K562 Cells
• Leukemia (pathology)
• NF-kappa B (metabolism)
• Spironolactone (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism
• Tumor Necrosis Factor-alpha (pharmacology)
• U937 Cells