ArticleOncotarget2016
Sirtuin 3 enhanced drug sensitivity of human hepatoma cells through glutathione S-transferase pi 1/JNK signaling pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Trial
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- Review
- SIRT3, a New Hope in Liver Diseases from Pathogenic Mechanisms to Therapeutic Strategies.Current pharmaceutical biotechnology · 2025Review
- Roles of SIRT3 in aging and aging-related diseases.International journal of biological sciences · 2025Review
- Sirtuin insights: bridging the gap between cellular processes and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Nicotinamide Riboside-Driven Modulation of SIRT3/mtROS/JNK Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury.International journal of medical sciences · 2024Article
- Mechanism of emodin in treating hepatitis B virus-associated hepatocellular carcinoma: network pharmacology and cell experiments.Frontiers in cellular and infection microbiology · 2024Article
- Succinate-Directed Approaches for Warburg Effect-Targeted Cancer Management, an Alternative to Current Treatments?Cancers · 2023Review
- The Role of NAD+, SIRTs Interactions in Stimulating and Counteracting Carcinogenesis.International journal of molecular sciences · 2023Review
- [Cigarette Smoke Induces Gefitinib Resistance in NSCLC Cells via ROS/Sirt3/SOD2 Pathway].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- Review
- The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance.Frontiers in oncology · 2022Review
- Modulation of SIRT3 expression through CDK4/6 enhances the anti-cancer effect of sorafenib in hepatocellular carcinoma cells.BMC cancer · 2020Article
- Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target.Theranostics · 2020Review
- Review
- Oridonin overcomes the gemcitabine resistant PANC-1/Gem cells by regulating GST pi and LRP/1 ERK/JNK signalling.OncoTargets and therapy · 2019Article
- High GSTP1 inhibits cell proliferation by reducing Akt phosphorylation and is associated with a better prognosis in hepatocellular carcinoma.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SIRT3, a class III histone deacetylase, has been implicated in various cancers as a novel therapeutic target. In hepatocellular carcinoma (HCC), we previously reported that SIRT3 induced cell apoptosis by regulating GSK-3β/Bax signaling pathway. Downregulation of SIRT3 in HCC cells facilitates tumor cell survival. In this study, we found that chemotherapeutic agents (doxorubicin, cisplatin and epirubicin) and sorafenib treatment downregulated SIRT3 mRNA and protein levels in three HCC cell lines. MTS assay found that SIRT3 overexpression sensitized liver cancer cells to chemotherapeutic agents and sorafenib in SMMC-7721, Huh-7 and PLC/PRF/5 cell lines. Moreover, SIRT3 overexpression promoted chemotherapeutic agents-induced or sorafenib-induced apoptosis as evidenced by flow cytometry, enhanced PARP cleavage and enhanced Caspase-9 cleavage in three HCC cells. In contrast, SIRT3 silencing increased drug resistance of HCC cells to chemotherapeutic agents. Mechanistic study found that SIRT3 downregulated the mRNA and protein levels of glutathione S-transferase pi 1 (GSTP1), which is a member of phase II detoxification enzymes families involved in metabolizing for chemotherapeutic agents. Moreover, SIRT3 decreased the amount of GSTP1 that was associated with JNK, which finally contributed the activation of JNK activity and activation of downstream target c-Jun and Bim. Importantly, GSTP1 overexpression or JNK inhibitor abolished SIRT3-induced apoptosis in HCC cells exposed to chemotherapeutic agents. Finally, there was a negative correlation between SIRT3 expression and GSTP1 expression in human HCC tissues. Together, our findings revealed SIRT3 could enhance the drug sensitivity of HCC cells to an array of chemotherapeutic agents. SIRT3 may serve as a potential target for improving the chemosensitivity of HCC patients.
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Registered trials
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.