# The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway

## TL;DR

This study shows that H2Valdien derivatives can stop liver cancer cell growth and reduce their spread by affecting a key signaling pathway.

## Contribution

The study reveals a novel mechanism by which H2Valdien derivatives inhibit EMT in hepatoma cells through the Hedgehog signaling pathway.

## Key findings

- H2Valdien derivatives induce apoptosis and growth arrest in hepatoma carcinoma cells.
- These derivatives reduce cell migration and invasion by modulating EMT-related proteins.
- They inhibit the Hedgehog signaling pathway by inactivating Sonic Hh and smoothened proteins.

## Abstract

This research delves into the influence of H2Valdien derivatives on the proliferation, migration, and apoptosis induction in hepatoma carcinoma cells (HepG2, Huh-7, and SMMC-7721), with a specific emphasis on inhibiting epithelial–mesenchymal transition (EMT) through modulation of the Hedgehog (Hh) signaling pathway. Utilizing the cell counting kit-8 method, flow cytometry, TUNEL assay, wound healing, and transwell assays, we observed a dose-dependent growth arrest and apoptosis induction in HepG2, Huh-7, and SMMC-7721 cells. Notably, H2Valdien derivatives exhibited a capacity to reduce migration and invasion, impacting the expression of EMT-associated proteins such as N-cadherin, vimentin, and E-cadherin. Mechanistically, these derivatives demonstrated the inhibition of the Hh signaling pathway by inactivating Sonic Hh (Shh) and smoothened proteins. This study underscores the robust antiproliferative and apoptosis-inducing effects of H2Valdien derivatives on hepatoma carcinoma cells and elucidates their regulatory role in EMT through modulation of the Hh signaling pathway, providing valuable insights for potential therapeutic interventions.