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Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine

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

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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
Status: Published
CreatorsEmailPitt UsernameORCID
Ke, Xiangyu
Qin, Qingsong
Deng, Tianyi
Liao, Yueyan
Gao, Shou-Jiangshg88@pitt.edushg88
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:
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


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