ArticlePloS one2014
Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- SIRT1 as a masterful reciprocal regulator of molecular mechanisms and signaling pathways involved in tumor growth and expansion.Clinical and experimental medicine · 2025Review
- The role of SIRT1 in the development of gastrointestinal tumors.Frontiers in cell and developmental biology · 2025Review
- SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis.Open medicine (Warsaw, Poland) · 2023Article
- Isoforms of the p53 Family and Gastric Cancer: A Ménage à Trois for an Unfinished Affair.Cancers · 2021Review
- Recent advances of SIRT1 and implications in chemotherapeutics resistance in cancer.American journal of cancer research · 2021Review
- Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy.Theranostics · 2021Article
- Epigenetic inhibitors target multiple stages of Plasmodium falciparum parasites.Scientific reports · 2020Article
- Heterogeneous Responses of Gastric Cancer Cell Lines to Tenovin-6 and Synergistic Effect with Chloroquine.Cancers · 2020Article
- The SIRT3 and SIRT6 Promote Prostate Cancer Progression by Inhibiting Necroptosis-Mediated Innate Immune Response.Journal of immunology research · 2020Article
- The Versatility of Sirtuin-1 in Endocrinology and Immunology.Frontiers in cell and developmental biology · 2020Review
- Generation of a novel model of primary human cell senescence through Tenovin-6 mediated inhibition of sirtuins.Biogerontology · 2019Article
- SIRT2 Promotes the Migration and Invasion of Gastric Cancer through RAS/ERK/JNK/MMP-9 Pathway by Increasing PEPCK1-Related Metabolism.Neoplasia (New York, N.Y.) · 2018Article
- The sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing's sarcoma cell line.Investigational new drugs · 2018Article
- Meta-analysis of SIRT1 expression as a prognostic marker for overall survival in gastrointestinal cancer.Oncotarget · 2017Article
- How to stomach an epigenetic insult: the gastric cancer epigenome.Nature reviews. Gastroenterology & hepatology · 2017Review
- Tenovin-6 inhibits proliferation and survival of diffuse large B-cell lymphoma cells by blocking autophagy.Oncotarget · 2017Article
- Tenovin-6 impairs autophagy by inhibiting autophagic flux.Cell death & disease · 2017Article
- Natural Killer Cell Response to Chemotherapy-Stressed Cancer Cells: Role in Tumor Immunosurveillance.Frontiers in immunology · 2017Review
- Sirtuin functions and modulation: from chemistry to the clinic.Clinical epigenetics · 2016Review
- Expression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients.PloS one · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Up-regulated sirtuin 1 (SIRT1), an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53). Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5). In the KatoIII cell line (TP53-null), DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.