# Bioactivity of Cyperus amuricus extracts against hepatocellular carcinoma and molecular docking analysis targeting the PI3K/AKT/mTOR pathway

## TL;DR

This study explores how Cyperus amuricus extracts fight liver cancer by targeting a key cancer pathway and shows promising results in cell tests.

## Contribution

The study combines in vitro assays and molecular docking to reveal how Cyperus amuricus compounds interact with the PI3K/AKT/mTOR pathway in hepatocellular carcinoma.

## Key findings

- The ethyl acetate fraction of Cyperus amuricus inhibited HepG2 cell proliferation with an IC50 of 159.76 µg/mL.
- Molecular docking showed strong binding affinities of Cyperus amuricus compounds to key proteins in the PI3K/AKT/mTOR pathway.
- Compounds like vitexin and digitoxin were found to target specific sites on AKT and mTOR with binding energies comparable to reference ligands.

## Abstract

Cyperus amuricus (Cyperaceae) has exhibited potential anticancer activity against hepatocellular carcinoma (HCC), yet its molecular mechanisms and phytoconstituent interactions with oncogenic pathways remain underexplored. This study integrates in vitro cytotoxicity assays and molecular docking to evaluate the effects of C. amuricus fractionated extracts on HCC, focusing on PI3K/AKT/mTOR signaling axis. The ethyl acetate (EA) fraction selectively inhibited HepG2 cell proliferation (IC50 = 159.76 µg/mL) with minimal toxicity to normal fibroblasts. Apoptotic features—cell shrinkage, membrane blebbing, nuclear condensation, and DNA fragmentation—were confirmed through DAPI staining and gel electrophoresis. Western blot analysis revealed dose-dependent suppression of phosphorylated Akt and p70S6K, indicating pathway inhibition. Molecular docking identified strong binding affinities between Cyperaceae-derived compounds and PI3K/AKT/mTOR targets, with luteolin 7-O-β-D-glucuronopyranoside-6″-methyl ester blocked PI3K activation, vitexin bound AKT’s allosteric site, and digitoxin targeted mTOR’s ATP-binding pocket, showing comparable binding energies to reference ligands. These findings suggest C. amuricus as a promising candidate for natural product-based HCC therapy.