| Title |
Targeting pancreatic cancer cells by a novel hydroxamate-based histone deacetylase (HDAC) inhibitor ST-3595
|
|---|---|
| Published in |
Tumor Biology, June 2015
|
| DOI | 10.1007/s13277-015-3537-5 |
| Pubmed ID | |
| Authors |
Shang Minjie, Hong Defei, Hu Zhimin, Wu Weiding, Zhang Yuhua |
| Abstract |
In the current study, we tested the potential anti-pancreatic cancer activity of a novel hydroxamate-based histone deacetylase (HDAC) inhibitor ST-3595. We showed that ST-3595 exerted potent anti-proliferative and cytotoxic activities against both established pancreatic cancer cell lines (PANC-1, AsPC-1, and Mia-PaCa-2), and patient-derived primary cancer cells. It was, however, generally safe to non-cancerous pancreatic epithelial HPDE6c7 cells. ST-3595-induced cytotoxicity to pancreatic cancer cells was associated with significant apoptosis activation. Reversely, the pan caspase inhibitor z-VAD-fmk and the caspase-8 inhibitor z-ITED-fmk alleviated ST-3595-mediated anti-pancreatic cancer activity in vitro. For the mechanism study, ST-3595 inhibited HDAC activity, and induced mitochondrial permeability transition pore (MPTP) opening in pancreatic cancer cells. Inhibition of MPTP, by cyclosporin A, sanglifehrin A, or by cyclophilin-D (Cyp-D) siRNA knockdown, dramatically inhibited ST-3595-induced pancreatic cancer cell apoptosis. Meanwhile, we found that a low concentration of ST-3595 dramatically sensitized gemcitabine-induced anti-pancreatic cancer cell activity in vitro. In vivo, ST-3595 oral administration inhibited PANC-1 xenograft growth in nude mice, and this activity was further enhanced when in combination with gemcitabine. In summary, the results of this study suggest that targeting HDACs by ST-3595 might represent as a novel and promising anti-pancreatic cancer strategy. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Sweden | 1 | 9% |
| Brazil | 1 | 9% |
| Unknown | 9 | 82% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 2 | 18% |
| Student > Master | 2 | 18% |
| Student > Bachelor | 2 | 18% |
| Other | 1 | 9% |
| Student > Doctoral Student | 1 | 9% |
| Other | 1 | 9% |
| Unknown | 2 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 3 | 27% |
| Agricultural and Biological Sciences | 2 | 18% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 9% |
| Biochemistry, Genetics and Molecular Biology | 1 | 9% |
| Immunology and Microbiology | 1 | 9% |
| Other | 1 | 9% |
| Unknown | 2 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 March 2016.
All research outputs
#18,449,393
of 22,858,915 outputs
Outputs from Tumor Biology
#1,369
of 2,622 outputs
Outputs of similar age
#189,807
of 264,433 outputs
Outputs of similar age from Tumor Biology
#67
of 159 outputs
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