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Published on: June 26, 2018
Growth-suppressive effect of suberoylanilide hydroxamic acid (SAHA) on human oral cancer cells
Boonsil Jang1, Ji-Ae Shin1, Yong-Soo Kim2
1Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience and Biodegradable Material, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
Purpose:
The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) has been reported to exhibit anticancer activities in various cancer cell types, but as yet there are few reports on the anticancer effects of SAHA in oral squamous cell carcinoma (OSCC)-derived cells and xenograft models.
Methods:
The anti-proliferative and apoptotic activities of SAHA were assessed in human HSC-3 and HSC-4 (OSCC)-derived cell lines and JB6 normal mouse skin-derived epidermal cells using histone acetylation, soft agar colony formation, trypan blue exclusion, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead viability/cytotoxicity and Western blot analyses.
Results:
We found that SAHA treatment resulted in hyperacetylation of histones H2A and H3 and a concomitant decrease in the viability of HSC-3 and HSC-4 cells. SAHA also significantly inhibited the neoplastic transformation of JB6 cells treated with TPA, whereas the viability of these cells was not affected by this treatment. Additionally, we found that SAHA suppressed the anchorage-independent growth (colony forming capacity in soft agar) of HSC-3 and HSC-4 cells. DAPI staining, Live/Dead and Western blot analyses revealed that SAHA can induce caspase-dependent apoptosis in HSC-3 and HSC-4 cells. We also found that SAHA treatment led to inhibition of ERK phosphorylation, and that two MEK inhibitors potentiated SAHA-mediated apoptosis. Okadaic acid treatment inhibited SAHA-mediated apoptosis in both the HSC-3 and HSC-4 cell lines, wheras SAHA induced a profound in vivo inhibition of tumor growth in HSC-3 xenografts.
Conclusions:
Our results indicate that the ERK signaling pathway may constitute a critical denominator of SAHA-induced apoptosis in OSCC-derived cells and that SAHA may have therapeutic potential for OSCC.
Insights
Suberoylanilide hydroxamic acid (SAHA) effectively reduces oral squamous cell carcinoma (OSCC) cell viability and induces apoptosis. SAHA shows therapeutic potential for OSCC by inhibiting tumor growth and targeting the ERK signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, demonstrates anticancer properties.
- Limited research exists on SAHA's effects in oral squamous cell carcinoma (OSCC) and related models.
Purpose of the Study:
- To investigate the anticancer effects of SAHA on OSCC-derived cells and xenografts.
- To explore the mechanisms underlying SAHA's action, including its impact on apoptosis and signaling pathways.
Main Methods:
- Assessed anti-proliferative and apoptotic activities of SAHA in HSC-3 and HSC-4 (OSCC) cells and JB6 epidermal cells.
- Utilized histone acetylation assays, soft agar colony formation, trypan blue exclusion, DAPI staining, Live/Dead viability assays, and Western blot analyses.
- Investigated the role of the ERK signaling pathway and MEK inhibitors in SAHA's effects.
Main Results:
- SAHA induced histone hyperacetylation and decreased viability in OSCC cells.
- SAHA inhibited neoplastic transformation and anchorage-independent growth of OSCC cells.
- SAHA triggered caspase-dependent apoptosis, inhibited ERK phosphorylation, and demonstrated significant in vivo tumor growth inhibition in HSC-3 xenografts.
Conclusions:
- SAHA exhibits significant anticancer activity against OSCC-derived cells and xenografts.
- The ERK signaling pathway is crucial for SAHA-induced apoptosis in OSCC.
- SAHA presents potential as a therapeutic agent for oral squamous cell carcinoma.
