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 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
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-regulated 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 have a persistent activation of caspase-3 in all the investigated systems,
while flavonoids circuitously affect the enzyme activity.