ArticleRedox biology2020
Melatonin sensitises shikonin-induced cancer cell death mediated by oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- Circadian rhythm disruption impairs ovarian follicular development via NADEBioMedicine · 2026Article
- PINK1 deacetylation by emodin-induced SIRT3 upregulation alleviates acute kidney injury by Inhibition of ferroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- 3-TYP protects against heart failure with preserved ejection fraction by inhibiting Sirtuin 3.Journal of molecular histology · 2025Article
- Synergistic inhibition of autophagic flux and induction of apoptosis in cervical cancer cells by Mito-TEMPO and hyperthermia.Environmental health and preventive medicine · 2025Article
- Melatonin and vitamin D as potential synergistic adjuvants for cancer therapy (Review).International journal of oncology · 2024Review
- Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging.Antioxidants (Basel, Switzerland) · 2023Review
- Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy.ACS biomaterials science & engineering · 2023Article
- Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1.Molecules (Basel, Switzerland) · 2023Review
- Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis.Cell death & disease · 2023Article
- Anti-proliferative effect of melatonin in human hepatoma HepG2 cells occurs mainly through cell cycle arrest and inflammation inhibition.Scientific reports · 2023Article
- PMCA inhibition reverses drug resistance in clinically refractory cancer patient-derived models.BMC medicine · 2023Article
- NEAT1-SOD2 Axis Confers Sorafenib and Lenvatinib Resistance by Activating AKT in Liver Cancer Cell Lines.Current issues in molecular biology · 2023Article
- Insights into Manganese Superoxide Dismutase and Human Diseases.International journal of molecular sciences · 2022Review
- Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 SignalingMolecules (Basel, Switzerland) · 2022Article
- Melatonin inhibits ESCC tumor growth by mitigating the HDAC7/β-catenin/c-Myc positive feedback loop and suppressing the USP10-maintained HDAC7 protein stability.Military Medical Research · 2022Article
- Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells.Antioxidants (Basel, Switzerland) · 2022Review
- Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma.International journal of molecular sciences · 2022Article
- Mitochondrial PKM2 deacetylation by procyanidin B2-induced SIRT3 upregulation alleviates lung ischemia/reperfusion injury.Cell death & disease · 2022Article
- A combined treatment with melatonin and andrographis promotes autophagy and anticancer activity in colorectal cancer.Carcinogenesis · 2022Article
- Review of Shikonin and Derivatives: Isolation, Chemistry, Biosynthesis, Pharmacology and Toxicology.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer.
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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 Socratic graph.