# H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer

**Authors:** Chunyan Dang, Shuping Ma, Xuhui Zhao, Ruilin Wang, Ruimin Liu, Hongling Li

PMC · DOI: 10.1515/med-2025-1208 · 2025-10-23

## TL;DR

H2valdien3, a water-soluble compound, stops gastric cancer cell growth by blocking the cell cycle and causing cell death.

## Contribution

H2valdien3 is a novel water-soluble derivative with anticancer effects on gastric cancer cells.

## Key findings

- H2valdien3 inhibits the proliferation of AGS and MKN45 gastric cancer cells.
- The compound induces apoptosis and arrests the cell cycle in these cells.
- Its mechanism involves the β-catenin/c-myc pathway and shows minimal side effects in mice.

## Abstract

Despite significant advances in the diagnosis and treatment of gastric cancer (GC), its incidence and mortality remain high worldwide. Therefore, finding new anticancer drugs or treatment strategies for GC is crucial. The valdien ligand, which is not soluble in water, has demonstrated potential anticancer effects on cancer. This study highlights a water-soluble derivative of the H2valdien ligand derivatives, named H2valdien3, which can inhibit the proliferation of GC by arresting the cell cycle and inducing apoptosis. Initially, the inhibitory effects and cytotoxicity of H2valdien3 on the growth of AGS and MKN45 cells were evaluated using MTT assays. Microscopic observations revealed that H2valdien3-treated AGS and MKN45 cells exhibited deteriorated morphology. Hoechst fluorescent staining and flow cytometry results further demonstrated that H2valdien3 promotes apoptosis and arrests the cell cycle in GC cells. Additionally, the anticancer mechanism of H2valdien3 was found to involve the β-catenin/c-myc pathway. In vivo experiments showed that H2valdien3 inhibited GC proliferation without significantly affecting the weight of the mice. These findings suggest that the transformed H2valdien3 has potential anticancer properties with minimal side effects for GC treatment.

## Linked entities

- **Genes:** ctnnb1.S (catenin beta 1 S homeolog) [NCBI Gene 380441], MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609]
- **Diseases:** gastric cancer (MONDO:0001056)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}
- **Diseases:** cancer (MESH:D009369), cytotoxicity (MESH:D064420), GC (MESH:D013274)
- **Chemicals:** water (MESH:D014867), H2valdien (-), MTT (MESH:C070243)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** AGS — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0139), MKN45 — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0434)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12552879/full.md

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Source: https://tomesphere.com/paper/PMC12552879