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Updated: Sep 5, 2025

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Published on: May 14, 2016
Trichodermin inhibits the growth of oral cancer through apoptosis-induced mitochondrial dysfunction and
Hsien-Lin Chen1, Yi-Hao Lo2, Chieh-Liang Lin3
1Division of General Surgery, Department of Surgery, Chi Mei Medical Center, Liouying, Tainan 73657, Taiwan.
Abstract:
Trichodermin (TCD), a trichothecene first isolated from marine Trichoderma viride, is an inhibitor of eukaryotic protein synthesis. However, the potential effects of TCD on human oral squamous cell carcinoma (OSCC) cells and the underlying molecular mechanisms remain unknown. In this study, the exposure of OSCC cells (Ca922 and HSC-3 cells) to TCD suppressed cell proliferation assessed using MTT assays and colony formation assays. TCD inhibited the migration and invasion of OSCC cells (Ca922 and HSC-3 cells) through the downregulation of matrix metalloproteinase 9. After treatment of OSCC cells with TCD, the G2/M phase was arrested, caspase-related apoptosis (cleaved caspase-3 and PARP expression) was induced, and the protein level of x-linked inhibitor of apoptosis was reduced. Meanwhile, the TCD-induced cell death was reversed by the pan-caspase inhibitor Z-VAD-FMK. Furthermore, TCD diminished mitochondrial membrane potential, mitochondrial oxidative phosphorylation and glycolytic function in OSCC cells. In addition, TCD decreased the levels of histone deacetylase 2 (HDAC-2) and downstream signaling proteins, including phosphorylated STAT3 and NF-κB. Finally, TCD significantly suppressed tumor growth in a zebrafish OSCC xenotransplantation model. Overall, this evidence demonstrates that TCD is a novel promising strategy for the treatment of OSCCs.
Insights
Trichodermin (TCD) effectively inhibits oral squamous cell carcinoma (OSCC) growth by suppressing proliferation, migration, and inducing apoptosis. This study highlights TCD as a potential therapeutic agent for OSCC treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Trichodermin (TCD), a trichothecene, is known to inhibit eukaryotic protein synthesis.
- The effects of TCD on oral squamous cell carcinoma (OSCC) and its mechanisms are not well understood.
Purpose of the Study:
- To investigate the anti-cancer effects of TCD on human OSCC cells.
- To elucidate the molecular mechanisms underlying TCD's action in OSCC.
Main Methods:
- MTT and colony formation assays for proliferation.
- Migration and invasion assays, Western blotting for protein analysis.
- Flow cytometry for cell cycle analysis, apoptosis assays, and mitochondrial function assessment.
- Zebrafish OSCC xenotransplantation model for in vivo efficacy.
Main Results:
- TCD suppressed OSCC cell proliferation, migration, and invasion by downregulating matrix metalloproteinase 9.
- TCD induced G2/M phase arrest and caspase-dependent apoptosis, while reducing x-linked inhibitor of apoptosis.
- TCD impaired mitochondrial function and decreased levels of HDAC-2, p-STAT3, and p-NF-κB.
- TCD significantly inhibited OSCC tumor growth in a zebrafish model.
Conclusions:
- TCD exhibits significant anti-cancer properties against OSCC cells in vitro and in vivo.
- TCD acts through multiple pathways, including apoptosis induction and metabolic dysfunction.
- TCD represents a promising novel therapeutic strategy for oral squamous cell carcinoma treatment.
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