ArticleCancer management and research2020
Melatonin Regulates Cisplatin Resistance and Glucose Metabolism Through Hippo Signaling in Hepatocellular Carcinoma Cells.
Article in Cancer management and research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Combined in vivo and silico assessment of melatonin's protective effects on rifampicin-induced liver damage in rats.Scientific reports · 2025Article
- A highly adhesive and melatonin-loaded PEG hydrogel prevents tumor recurrence and promotes wound healing for tumor-resection wound management of liposarcoma.Materials today. Bio · 2025Article
- Mechanisms of drug resistance in hepatocellular carcinoma.Biological procedures online · 2025Review
- Effects of melatonin in polycystic ovary syndrome: is there Hippo pathway crosstalk?Journal of ovarian research · 2025Review
- The melatonin-FTO-ATF4 signaling pathway protects granulosa cells from cisplatin-induced chemotherapeutic toxicity by suppressing ferroptosis.Journal of assisted reproduction and genetics · 2024Article
- The role of glypican-3 in hepatocellular carcinoma: Insights into diagnosis and therapeutic potential.European journal of medical research · 2024Review
- The activation of the Notch signaling pathway by UBE2C promotes the proliferation and metastasis of hepatocellular carcinoma.Scientific reports · 2024Article
- Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.Cell communication and signaling : CCS · 2023Review
- Advances in prognostic and therapeutic targets for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The hippo signaling pathway.Frontiers in oncology · 2022Review
- Therapeutic Effect of Melatonin in Premature Ovarian Insufficiency: Hippo Pathway Is Involved.Oxidative medicine and cellular longevity · 2022Review
- Review
- Melatonin as an Antitumor Agent against Liver Cancer: An Updated Systematic Review.Antioxidants (Basel, Switzerland) · 2021Review
- A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer.Frontiers in oncology · 2021Review
- Role and Therapeutic Potential of Melatonin in Various Type of Cancers.OncoTargets and therapy · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
INTRODUCTION AND
aimHepatocellular carcinoma (HCC) is a primary malignancy that occurs in the liver. Clinical cases have been recorded worldwide, particularly in the Saharan area and Asia. In the present work, we aimed to probe the characteristics of melatonin involved in human HCC development, especially in cisplatin resistance and glucose metabolism.
methodsTwo HCC cells, HepG2 and Hep3B cells, were treated with melatonin. Cell cycle test was then used to define the role of melatonin in cell progression while Western blotting and qPCR assay were applied to determine the associated proteins in the treatment. Annexin V/PI staining and MTT assay was used to probe the involvement of melatonin in cisplatin-induced cell apoptosis process. Successively, we assessed glucose consumption in melatonin treated cells along with Western blotting for detection of GLUT-3 expression level. Yes-associated protein (YAP), a key regulator of Hippo signaling pathway, was further examined to characterize the function of melatonin on adjusting GLUT3 and Bcl-2 expression.
resultsMelatonin enabled inhibition of HepG2 and Hep3B proliferation and cell cycle progression via affecting the cell cycle-associated proteins. Annexin V/PI staining and MTT assay results demonstrated that melatonin assisted cisplatin-induced apoptosis accompanied with upregulated caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, as well as Bcl-2 expression. It revealed that melatonin inhibits glucose uptake and ATP production via downregulation of Glucose transporter 3 (GLUT3). In addition, YAP was downregulated by melatonin treatment. The YAP depletion in HepG2 and Hep3B cells suppressed mRNA and protein expression of Bcl-2 and GLUT3, whereas overexpression of YAP in melatonin treated cells partly reversed the melatonin-induced inhibition on proliferation, cisplatin-induced apoptosis, and GLUT3 and Bcl-2 expression.
conclusionMelatonin hindered HCC proliferation and aided cisplatin resistance via regulating the Hippo signaling pathway.
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