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Article

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

1
Laboratory of Human Virology and Oncology, Shantou University Medical College, Shantou 515000, China
2
UPMC Hillman Cancer Center, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(2), 365; https://doi.org/10.3390/cancers12020365
Received: 7 January 2020 / Revised: 14 January 2020 / Accepted: 2 February 2020 / Published: 5 February 2020
(This article belongs to the Collection Drug Resistance and Novel Therapies in Cancers)
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. View Full-Text
Keywords: Gastric cancer; Epstein–Barr virus (EBV); Tenovin-6; chloroquine; autophagy; p53 activation Gastric cancer; Epstein–Barr virus (EBV); Tenovin-6; chloroquine; autophagy; p53 activation
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MDPI and ACS Style

Ke, X.; Qin, Q.; Deng, T.; Liao, Y.; Gao, S.-J. Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine. Cancers 2020, 12, 365. https://doi.org/10.3390/cancers12020365

AMA Style

Ke X, Qin Q, Deng T, Liao Y, Gao S-J. Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine. Cancers. 2020; 12(2):365. https://doi.org/10.3390/cancers12020365

Chicago/Turabian Style

Ke, Xiangyu, Qingsong Qin, Tianyi Deng, Yueyan Liao, and Shou-Jiang Gao. 2020. "Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine" Cancers 12, no. 2: 365. https://doi.org/10.3390/cancers12020365

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