Positive Health Online
Your Country
![[Image: http://www.abundanceandhealth.co.uk]](/img/original/BannerAvatar/2836.df7d2315253110ff5b3a566f94871f99.jpg "http://www.abundanceandhealth.co.uk")
![[Image: https://www.water-for-health.co.uk/]](/img/original/BannerAvatar/4046.12831f50177f8848ee87b8e94411d6b3.jpg "https://www.water-for-health.co.uk/")
![[Image: http://www.balens.co.uk]](/img/original/BannerAvatar/2148.50367fa908013fae0a7f1a171543ef92.jpg "http://www.balens.co.uk")
![[Image: http://www.drsgoodman.com/books-goodman/52-nutrition-and-cancer]](/img/original/BannerAvatar/1859.1296090fd8385e7ceff51c8011559097.jpg "http://www.drsgoodman.com/books-goodman/52-nutrition-and-cancer")
Research: FENG and COLLEAGUES,
Listed in Issue 234
Abstract
FENG and COLLEAGUES, (1)Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Shandong, China ; Anhui Province Key Laboratory of Molecular Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui, China investigated, at the molecular level, the role of histone acetylation in cancer with regard to the epigenetic silencing of tumour suppressor genes (TSGs).
Background
Aberrant histone acetylation plays an essential role in the neoplastic process via the epigenetic silencing of tumour suppressor genes (TSGs); therefore, the inhibition of histone deacetylases (HDAC) has become a promising target in cancer therapeutics.
Methodology
To investigate the correlation of histone acetylation with clinicopathological features and TSG expression, the authors examined the expression of acetylated H3 (AcH3), RARβ2, E-cadherin, and β-catenin by immunohistochemistry in 65 cervical squamous cell carcinoma patients.
Results
The results revealed that the absence of AcH3 was directly associated with poor histological differentiation and nodal metastasis as well as reduced/negative expression of RARβ2, E-cadherin, and β-catenin in clinical tumour samples. They further demonstrated that the clinically available HDAC inhibitors valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), in combination with all-trans retinoic acid (ATRA), can overcome the epigenetic barriers to transcription of RARβ2 in human cervical cancer cells. Chromatin immuno-precipitation analysis showed that the combination treatment increased the enrichment of acetylated histone in the RARβ2-RARE promoter region. In view of these findings, we evaluated the antitumor effects induced by combined VPA and ATRA treatment in a xenograft model implanted with poorly differentiated human squamous cell carcinoma. Notably, VPA restored RARβ2 expression via epigenetic modulation. Additive antitumour effects were produced in tumour xenografts by combining VPA with ATRA treatment. Mechanistically, the combination treatment reactivated the expression of TSGs RARβ2, E-cadherin, P21 (CIP1) , and P53 and reduced the level of p-Stat3. Sequentially, upregulation of involucrin and loricrin, which indicate terminal differentiation, strongly contributed to tumour growth inhibition along with partial apoptosis.
Conclusion
In conclusion, targeted therapy with HDAC inhibitors and RARβ2 agonists may represent a novel therapeutic approach for patients with cervical squamous cell carcinoma.
References
Feng D(1), Wu J, Tian Y, Zhou H, Zhou Y, Hu W, Zhao W, Wei H, Ling B, Ma C. eCollection 2013. Targeting of histone deacetylases to reactivate tumour suppressor genes and its therapeutic potential in a human cervical cancer xenograft model. PLoS One.;8(11):e80657. doi: 10.1371/journal.pone.0080657. Nov 19 2013.
Comment
The above research which merits our utmost attention, indicates unequivocally that histone deacetylases (HDAC) have the ability modulate - upregulate as well as inhibit - expression of a range of tumour activation and suppressor genes.
