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 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-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.

背景：Caspase-3负责细胞凋亡的执行。近来，作为发现天然产物作为抗癌剂的有希望的目标，它已引起注意。

方法：我们采用计算机模拟，无细胞和基于细胞的活性以及实时基因表达分析，研究了两组不同的天然产物（类萜和类黄酮）对caspase-3活性的功效。

结果：观察到萜烯在无细胞和基于细胞的系统中均激活caspase-3活性，这由基因表达分析，结合能和激活常数支持。但是，类黄酮的作用仅限于基于细胞的系统，转录调控表明它们是间接结合的，这增强了酶的活性并上调了细胞中mRNA的表达。在测试的天然产物中，观察到（+）香芹酮是K562（34.4μM），WRL-68（22.3μM），HeLa（18.7μM），MCF-7（39.4μM）和MDA-MB-231细胞系（45.1μM）。

结论：总的来说，萜烯类化合物在所有研究的系统中都具有caspase-3的持久活化作用，而类黄酮circuit回影响酶的活性。