Prenylated flavonoids from Ficus hirta induces HeLa cells apoptosis via MAPK and AKT signaling pathways

https://doi.org/10.1016/j.bmcl.2021.127859Get rights and content

Highlights

  • A pair of undescribed enantiomers (1a/1b) was isolated from the roots of Ficus hirta.

  • Compound 4 showed enhanced cytotoxicity on HeLa, MCF-7 and H460 cells.

  • Compound 4 induced HeLa cells apoptosis and increased the PARP cleavage.

  • Compound 4 increased the expression of p-JNK and p-p38.

  • Compound 4 reduced the protein levels of p-AKT and p-ERK.

Abstract

A pair of undescribed enantiomers, (±) ficusflavonid A (1a/1b), along with five known analogues, were isolated from the roots of Ficus hirta. Their structures were determined by the analysis of extensive spectroscopic data (including UV, IR, HRESIMS and NMR). Two enantiomers (1a and 1b) were successfully separated by chiral chromatographic column and their absolute configurations were assigned by the comparison of experimental and calculated ECD data. The cytotoxicity of all the isolates against HeLa, MCF-7, HepG2 and H460 cell lines were evaluated by MTT assay. Among them, 4 suppressed the proliferation of HeLa cells with the IC50 value of 28.88 μM. Furthermore, the apoptotic effect of 4 on HeLa cells and the level of several crucial proteins in AKT/MAPKs signaling pathways were analyzed by flow cytometer and western blot assay. As a result, 4 induced HeLa cell apoptosis in a dose dependent manner and significantly increased the protein levels of p-JNK and p-p38, whereas distinctly reduced the expression of p-AKT, and p-ERK. Thus, compound 4 might induce HeLa cells apoptosis via MAPK and AKT signaling pathways, which could be considered as a potential leading compound for the development of anticancer drugs.

Section snippets

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was supported by grants from the Natural Science Foundation of China (NSFC) (Nos. 81773866, 81771377 and U1705285), Fundamental Research Funds for the Central Universities (No. 20720190079) and Natural Science Foundation of Fujian Province of China (No. 2019J007).

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