Trichodermin inhibits the growth of oral cancer through apoptosis-induced mitochondrial dysfunction and HDAC-2-mediated signaling
- PMID: 35785707
- DOI: 10.1016/j.biopha.2022.113351
Trichodermin inhibits the growth of oral cancer through apoptosis-induced mitochondrial dysfunction and HDAC-2-mediated signaling
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.
Keywords: HDAC-2; Migration; Mitochondrial oxidative phosphorylation; Oral squamous cell carcinoma; Trichodermin.
Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Conflict of interest statement
Conflict of interest statement The authors declare that they have no competing interests.
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