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

摘要

Background/Aim: NF-kappa B affects most aspects of cellular physiology. Deregulation of NF-kappa B signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-kappa B 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-methyllactonecyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-alpha-induced NF-kappa B 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 NFkB inhibition activity in leukemia cancer cells.