Activation of caspase-3 by terpenoids and flavonoids in different types of cancer cells

Background: Caspase-3 is accountable for the execution of apoptosis. Recently, it has gained attention as a promising target for the discovery of natural products as anticancer agents.

Methods: We have examined the efficacy of two different sets of natural products (terpenoids and flavonoids) towards caspase-3 activity adopting in silico, cell-free and cell-based activity and real-time gene expression analysis.

Results: It was observed that terpenes activate caspase-3 activity in both the cell-free and cell-based systems, which was supported by the gene expression analysis, binding energy and activation constant. Flavonoids action, however, was limited to the cell-based system and transcriptional regulation suggesting their indirect association, which enhanced the enzyme activity and up-regulate the expression of mRNA levels in the cells. Among the tested natural products, (+) carvone, was observed to be the best activator of caspase-3 in K562 (34.4 μM), WRL-68 (22.3 μM), HeLa (18.7 μM), MCF-7 (39.4 μM) and MDA-MB-231 cell lines (45.1 μM).

Conclusion: Overall, terpenoids had a persistent activation of caspase-3 in all the investigated system while flavonoids circuitously affect the enzyme activity.

Keywords: Caspase-3; activation constant; binding energy; flavonoids; molecular interaction; terpenoids.