ArticleCancer medicine2018
Novel therapeutic roles of MC-4 in combination with everolimus against advanced renal cell carcinoma by dual targeting of Akt/pyruvate kinase muscle isozyme M2 and mechanistic target of rapamycin complex 1 pathways.
Article in Cancer medicine, 2018. 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, 22 citations in OpenAlex.
- Molecular mechanisms of renal cell carcinoma metastasis and potential targets for therapy.Frontiers in cell and developmental biology · 2025Review
- Artemisiae Annuae Herba: from anti-malarial legacy to emerging anti-cancer potential.Theranostics · 2025Review
- Triple negative breast cancer migration is modified by mitochondrial metabolism alteration induced by natural extracts of C. spinosa and P. alliacea.Scientific reports · 2024Article
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
- Expression of AKT1 Related with Clinicopathological Parameters in Clear Cell Renal Cell Carcinoma.Current issues in molecular biology · 2022Article
- Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies.Cancers · 2022Review
- Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells.International journal of molecular sciences · 2022Review
- Therapeutic Potential of Natural Products in the Treatment of Renal Cell Carcinoma: A Review.Nutrients · 2022Review
- Overexpression of PFKFB3 promotes cell glycolysis and proliferation in renal cell carcinoma.BMC cancer · 2022Article
- A Simple-To-Use Nomogram for Predicting Early Death in Metastatic Renal Cell Carcinoma: A Population-Based Study.Frontiers in surgery · 2022Article
- Biological Evaluation of Oxindole Derivative as a Novel Anticancer Agent against Human Kidney Carcinoma Cells.Biomolecules · 2020Article
- Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma.International journal of molecular sciences · 2019Article
- Knockdown of PKM2 enhances radiosensitivity of cervical cancer cells.Cancer cell international · 2019Article
- Chemical Screening Approaches Enabling Drug Discovery of Autophagy Modulators for Biomedical Applications in Human Diseases.Frontiers in cell and developmental biology · 2019Review
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Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current clinical trials of new anticancer therapies against metastatic renal cell carcinoma (RCC), including molecular-targeted therapies, have not shown promise. The purpose of this study was to preclinically assess the antitumor effects of MC-4, a partially purified material of Artemisia annua L., as a monotherapy or in combination with the known mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, everolimus, against Caki-1 (Von Hippel-Lindau (VHL)+/+) and 786-O (VHL-/-) human RCC cells. MC-4 monotherapy significantly increased tumor growth inhibition and autophagic cell death in RCC cells in vitro and in vivo. Everolimus led to compensatory Akt activation by inhibiting only mTORC1 signaling pathway. In contrast to everolimus, MC-4 enhanced phosphatase and tensin homolog expression and reduced its downstream effector, Akt/pyruvate kinase muscle isozyme M2 (PKM2), leading to decreased expression of glucose transporter 1, which is associated with cancer cell metabolism. The synergistic antitumor and anti-metastatic effects induced by co-administration of MC-4 and everolimus involve cell growth inhibition and autophagic cell death via dual targeting of phosphatidylinositol 3-kinase (PI3K)/Akt/PKM2 and mTORC1. These findings suggest that MC-4 is a novel Akt/PKM2 inhibitor that can overcome the limitation of existing mTOR inhibitors and can be considered a novel strategy to treat patients with rapidly progressing advanced RCC.
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