Abstract
Background and Objective: Epigenetic modifications are believed to play a significant role in the development of cancer progression, growth, differentiation, and cell death. One of the most popular histone deacetylases inhibitors (HDACIs), suberoylanilide hydroxamic acid (SAHA), also known as Vorinostat, can directly activate p21WAF1/CIP1 gene transcription through hyperacetyla-tion of histones by a p53 independent mechanism. In the present investigation, we evaluated the correlation between histone modifications and DNA methyltransferase enzyme levels following SAHA treatments in A2780 ovarian cancer cells. Materials and Methods: Acetylation of histones and methyltransferases levels were analyzed using RT2 profiler PCR array, immunoblotting, and immunofluorescence methods in 2D and 3D cell culture systems. Results: The inhibition of histone deacetylases (HDAC) activities by SAHA can reduce DNA methyl transferases/histone methyl transferases (DNMTs/HMTs) levels through induction of hyperacetylation of histones. Immunofluo-rescence analysis of cells growing in monolayers and spheroids revealed significant up-regulation of histone acetylation preceding the above-described changes. Conclusions: Our results depict an interesting interplay between histone hyperacetylation and a decrease in methyltransferase levels in ovarian cancer cells, which may have a positive impact on the overall outcomes of cancer treatment.
| Original language | English |
|---|---|
| Article number | 456 |
| Journal | Medicina (Lithuania) |
| Volume | 57 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2021 |
Bibliographical note
Publisher Copyright:© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Funding
This research was supported by the Royal Dames of Cancer Research Inc. of Fort Lauderdale, FL, USA.
ASJC Scopus Subject Areas
- General Medicine
Keywords
- DNA methyltransferase
- Epigenetic alterations
- Histone modifications
- P21
- SAHA
Disciplines
- Medicine and Health Sciences