Abstract
Selective Histone Acetylation Inhibitors Reduce Pancreatic Cancer Cell Growth and Induces Apoptosis via Downregulating the NFκB Pathway
Journal of the American College of Surgeons, Vol.223(4), pp.S144-S144
10/2016
DOI: 10.1016/j.jamcollsurg.2016.06.306
Abstract
Introduction
Post-translation modification of histones plays an important role in carcinogenesis. Histone acetyltransferases (HAT) are the enzymes that are primarily responsible for histone acetylation resulting in transcriptional activation. The aim of this study was to evaluate HAT inhibitors as novel therapy against pancreatic cancer.
Methods
HAT was inhibited in pancreatic cancer cell line MiaPaCa-2 and S2VP10 cells by C646; selective histone acetyl transferase inhibitors and cell viability, apoptosis, and cell cycle were evaluated. Because NFκB activity is important for survival of pancreatic cancer and because histone acetylation is important for NFκB activation, we evaluated the impact of HAT inhibition on NFκB activity, as measured by dual reporter luciferase assay.
Results
C646 (0-100 μM) resulted in a dose- and time-dependent cytotoxicity in MiaPaCa-2 and S2VP10 cells, with a corresponding increase in caspase-3 cleavage (measured by flow cytometry). The IC-50 (μM) for C646 at 72 hours was 50±3.2 and 10±1.3 for MiaPaCa-2 and S2VP10 cells, respectively. C646 also induced G2/M phase arrest in pancreatic cancer cell lines. C646 selectively decreased levels of acetylated Histone-3 and Histone-4. We observed that HAT inhibition with C646 led to decreased NFκB activity in a dose-dependent fashion.
Conclusions
Histone acetyl transferase inhibition leads to pancreatic cancer cell death and NFκB inhibition. HAT inhibitors could emerge as a novel therapeutic strategy, either alone or in combination with other chemotherapeutics.
Details
- Title: Subtitle
- Selective Histone Acetylation Inhibitors Reduce Pancreatic Cancer Cell Growth and Induces Apoptosis via Downregulating the NFκB Pathway
- Creators
- Bhuwan Giri - University of MiamiShrey Modi - University of MiamiJohn George - University of MiamiVrishketan Sethi - University of MiamiBharti Garg - University of MiamiSulagna Banerjee - University of MiamiMahender K. Singh - University of MiamiAshok Saluja - University of MiamiVikas Dudeja - University of Miami
- Resource Type
- Abstract
- Publication Details
- Journal of the American College of Surgeons, Vol.223(4), pp.S144-S144
- DOI
- 10.1016/j.jamcollsurg.2016.06.306
- ISSN
- 1072-7515
- eISSN
- 1879-1190
- Publisher
- ELSEVIER SCIENCE INC
- Language
- English
- Date published
- 10/2016
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9985244565402771
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