# Cytotoxic Mechanism of Deep-Sea Fungus Chaetomium globosum YP-106 Metabolite Chaetomugilin O in Thyroid Cancer Cells

## TL;DR

A compound from a deep-sea fungus shows promise in fighting thyroid cancer by stopping cell growth and triggering cell death.

## Contribution

Chaetomugilin O's antitumor mechanism through ROS, cell cycle arrest, and Akt inhibition in thyroid cancer is newly characterized.

## Key findings

- Chaetomugilin O inhibits thyroid cancer cell proliferation with an IC50 of 13.57 µM.
- The compound induces ROS accumulation, G2/M phase arrest, and apoptosis in cancer cells.
- Molecular docking shows chaetomugilin O binds to Akt, suggesting inhibition of the PI3K-Akt pathway.

## Abstract

This study investigated the potential of the deep-sea-derived fungal metabolite, chlorinated azaphilone compound chaetomugilin O, in the treatment of thyroid cancer. Chaetomugilin O was extracted from the fungus Chaetomium globosum YP-106 and subjected to in vitro experiments. The results demonstrated that this compound significantly inhibited the proliferation of thyroid cancer CAL-62 cells in a dose-dependent manner, with an IC50 value of 13.57 µM. Further mechanistic studies revealed that chaetomugilin O exerts its antitumor effects by inducing reactive oxygen species (ROS) accumulation, G2/M phase cell cycle arrest, and apoptosis. Transcriptomic analysis indicated its regulatory role in the PI3K-Akt signaling pathway, suggesting a multi-target synergistic antitumor mechanism. Molecular docking confirmed that chaetomugilin O binds to the Akt protein, forming a hydrogen bond with Lys158, implying its potential to directly inhibit Akt activity and interfere with PI3K-Akt pathway function. This study provides experimental evidence for the development of novel, low-toxicity, highly effective therapeutic agents for thyroid cancer.