Ke, Xiangyu and Qin, Qingsong and Deng, Tianyi and Liao, Yueyan and Gao, Shou-Jiang
(2020)
Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine.
Cancers, 12 (2).
p. 365.
ISSN 2072-6694
Abstract
Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death. Approximately 15% of GC is associated with Epstein–Barr virus (EBV). GC is largely incurable with a dismal five-year survival rate. There is an urgent need to identify new therapeutic agents for the treatment of GC. Tenovin-6 was initially identified as a p53 activator, but it was later found to inhibit autophagy flux, and the protein deacetylase activity of sirtuins. Tenovin-6 shows promising therapeutic effect in various malignancies. However, it remains unknown whether Tenovin-6 is effective for GC. In this study, we found that EBV-positive and -negative GC cell lines were sensitive to Tenovin-6 but with different response times and doses. Tenovin-6 suppressed anchorage-independent growth of GC cells. Tenovin-6 induced different levels of apoptosis and phases of cell-cycle arrest depending on the cell lines with some manifesting gap 1 (G1) and others showing synthesis (S) phase cell-cycle arrest. Mechanistically, Tenovin-6 induced autophagy or p53 activation in GC cells depending on the status of TP53 gene. However, initiation of autophagy following treatment with Tenovin-6 conferred some protective effect on numerous cells. Combined treatment with Tenovin-6 and autophagy inhibitor chloroquine increased the cytotoxic effect by inducing microtubule-associated protein 1 light chain 3B (LC3B)-II accumulation, and by enhancing apoptosis and cell-cycle arrest. These results indicated that Tenovin-6 can be used as a potential therapeutic agent for GC, but the genetic background of the cancer cells might determine the response and mechanism of action. Treatment with Tenovin-6 alone or in combination with chloroquine could be a promising therapeutic approach for GC
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
---|
Ke, Xiangyu | | | | Qin, Qingsong | | | | Deng, Tianyi | | | | Liao, Yueyan | | | | Gao, Shou-Jiang | shg88@pitt.edu | shg88 | |
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Centers: |
Other Centers, Institutes, Offices, or Units > Hillman Cancer Center |
Date: |
5 February 2020 |
Date Type: |
Publication |
Journal or Publication Title: |
Cancers |
Volume: |
12 |
Number: |
2 |
Publisher: |
MDPI AG |
Page Range: |
p. 365 |
DOI or Unique Handle: |
10.3390/cancers12020365 |
Schools and Programs: |
School of Medicine > Microbiology and Molecular Genetics |
Refereed: |
Yes |
Uncontrolled Keywords: |
gastric cancer, epstein–barr virus (ebv), tenovin-6, chloroquine, autophagy, p53 activation |
ISSN: |
2072-6694 |
Official URL: |
http://dx.doi.org/10.3390/cancers12020365 |
Funders: |
Department of Education of Guangdong province in China, Natural Science Foundation of department of Science and Technology, Guangdong, China |
Article Type: |
Research Article |
Date Deposited: |
11 Jun 2021 20:32 |
Last Modified: |
11 Jun 2021 20:32 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/41276 |
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