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Current Topics in Medicinal Chemistry

Author(s): Nusrat Masood, Vijaya Dubey and Suaib Luqman*

DOI: 10.2174/1568026620666200710101859

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Activation of Caspase-3 by Terpenoids and Flavonoids in Different Types of Cancer Cells

Page: [1876 - 1887] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

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.

Keywords: Caspase-3, Flavonoids, Terpenoids, Molecular interaction, Binding energy, Activation constant.

Graphical Abstract

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