PUBLICATION
Trichodermin inhibits the growth of oral cancer through apoptosis-induced mitochondrial dysfunction and HDAC-2-mediated signaling
- Authors
- Chen, H.L., Lo, Y.H., Lin, C.L., Lee, T.H., Leung, W., Wang, S.W., Lin, I.P., Lin, M.Y., Lee, C.H.
- ID
- ZDB-PUB-220706-12
- Date
- 2022
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 153: 113351 (Journal)
- Registered Authors
- Keywords
- HDAC-2, Migration, Mitochondrial oxidative phosphorylation, Oral squamous cell carcinoma, Trichodermin
- MeSH Terms
-
- Animals
- Apoptosis
- Carcinoma, Squamous Cell*/pathology
- Caspases/metabolism
- Cell Line, Tumor
- Cell Proliferation
- Histone Deacetylase 2
- Humans
- Mitochondria/metabolism
- Mouth Neoplasms*/pathology
- Trichodermin/pharmacology
- Zebrafish/metabolism
- PubMed
- 35785707 Full text @ Biomed. Pharmacother.
Citation
Chen, H.L., Lo, Y.H., Lin, C.L., Lee, T.H., Leung, W., Wang, S.W., Lin, I.P., Lin, M.Y., Lee, C.H. (2022) Trichodermin inhibits the growth of oral cancer through apoptosis-induced mitochondrial dysfunction and HDAC-2-mediated signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 153:113351.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping