ArticleCancer biology & medicine2021
Nobiletin downregulates the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma.
Article in Cancer biology & medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Effects of polyphenols on cancer cell progression mediated by inhibition of cyclin-dependent kinases (CDKs): the emerging drug targets in cancer.Archives of pharmacal research · 2025Review
- Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment.Biomolecules · 2025Review
- E3 ligase Skp2-mediated stabilization of survivin contributes to radioresistance.Cell death discovery · 2025Article
- Nobiletin mitigates benign prostatic hyperplasia by suppressing prostate cell proliferation through regulation of cell cycle progression, signaling pathways, transcription factor activity, and the androgen-signaling axis.Frontiers in pharmacology · 2025Article
- E3 ubiquitin ligase on the biological properties of hematopoietic stem cell.Journal of molecular medicine (Berlin, Germany) · 2023Review
- The mycelium of the Trametes versicolor synn. Coriolus versicolor (Turkey tail mushroom) exhibit anti-melanoma activity in vitro.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- A review on the role of cyclin dependent kinases in cancers.Cancer cell international · 2022Review
- An Integrative Pan-Cancer Analysis Revealing MLN4924 (Pevonedistat) as a Potential Therapeutic Agent Targeting Skp2 in YAP-Driven Cancers.Frontiers in genetics · 2022Article
- Aqueous Extract and Polysaccharide of Aconiti Lateralis Radix Induce Apoptosis and G0/G1 Phase Cell Cycle Arrest by PI3K/AKT/mTOR Signaling Pathway in Mesangial Cells.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- A Novel Prognostic Predictor of Immune Microenvironment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature.International journal of medical sciences · 2022Article
- NEDD4L-induced ubiquitination mediating UBE2T degradation inhibits progression of lung adenocarcinoma via PI3K-AKT signaling.Cancer cell international · 2021Article
- Selective degradation of AR-V7 to overcome castration resistance of prostate cancer.Cell death & disease · 2021Article
- Identification of CDK2-Related Immune Forecast Model and ceRNA in Lung Adenocarcinoma, a Pan-Cancer Analysis.Frontiers in cell and developmental biology · 2021Article
- CircCRIM1 Promotes Hepatocellular Carcinoma Proliferation and Angiogenesis by Sponging miR-378a-3p and Regulating SKP2 Expression.Frontiers in cell and developmental biology · 2021Article
- SKP2 E3 ligase in urological malignancies: a critical regulator of the cell cycle and therapeutic target.Cell cycle (Georgetown, Tex.)Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Natural extracts, including nobiletin, have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs. However, whether and how nobiletin affects tumor growth and progression in renal cell carcinoma (RCC) are still unclear. Methods: Cell proliferation, cell cycle and apoptosis analyses, colony-formation assays, immunoblotting analysis, and qRT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation Results: Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells. Mechanistically, nobiletin decreased SKP2 protein expression by reducing its transcriptional level. The downregulated SKP2 caused accumulation of its substrates, p27 and p21, which further inhibited the activity of the G1 phase-related protein, CDK2, leading to inhibition of cell proliferation and tumor formation. A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor, palbociclib. A combination of nobiletin and palbociclib showed a synergistic tumor inhibition Conclusions: Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor, palbociclib, on RCC, which indicates a potential new therapeutic strategy.
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