ArticleBritish journal of pharmacology2012
Prodigiosin down-regulates SKP2 to induce p27(KIP1) stabilization and antiproliferation in human lung adenocarcinoma cells.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Promising Prodiginins Biological Activities.Chemistry & biodiversity · 2025Review
- Evaluation of the Combinatory Anticancer Effect of Chemotherapeutic Compounds and Prodigiosin against HCT-116, LoVo, and A549 Cell lines.ACS omega · 2024Article
- Rational Design of Nanomedicine for Placental Disorders: Birthing a New Era in Women's Reproductive Health.Small (Weinheim an der Bergstrasse, Germany) · 2024Review
- Identification of Novel Protein Targets of Prodigiosin for Breast Cancer Using Inverse Virtual Screening Methods.Applied biochemistry and biotechnology · 2023Article
- Rise of the natural red pigment 'prodigiosin' as an immunomodulator in cancer.Cancer cell international · 2022Review
- Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway.Scientific reports · 2022Article
- miR-590-5p Targets Skp2 to Inhibit the Growth and Invasion of Malignant Melanoma Cells.Disease markers · 2022Article
- Effects ofJournal of microbiology and biotechnology · 2021Article
- Nobiletin downregulates the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and shows synergistic effects with palbociclib on renal cell carcinoma.Cancer biology & medicine · 2021Article
- Production and Potential Applications of Bioconversion of Chitin and Protein-Containing Fishery Byproducts into Prodigiosin: A Review.Molecules (Basel, Switzerland) · 2020Review
- Cytotoxic Effect of Prodigiosin, Natural Red Pigment, Isolated fromIndian journal of microbiology · 2020Article
- Targeted Delivery Prodigiosin to Choriocarcinoma by Peptide-Guided Dendrigraft Poly-l-lysines Nanoparticles.International journal of molecular sciences · 2019Article
- The Natural Product Butylcycloheptyl Prodiginine Binds Pre-miR-21, Inhibits Dicer-Mediated Processing of Pre-miR-21, and Blocks Cellular Proliferation.Cell chemical biology · 2019Article
- Genotoxic activity of L-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420.World journal of microbiology & biotechnology · 2019Article
- SKP2 targeted inhibition suppresses human uveal melanoma progression by blocking ubiquitylation of p27.OncoTargets and therapy · 2019Article
- A Soft Coral-Derived Compound, 11-Dehydrosinulariolide, Induces G2/M Cell Cycle Arrest and Apoptosis in Small Cell Lung Cancer.Marine drugs · 2018Article
- Biological Potential and Mechanism of Prodigiosin fromInternational journal of molecular sciences · 2018Article
- Comparative Transcriptomics Unravels Prodigiosin's Potential Cancer-Specific Activity Between Human Small Airway Epithelial Cells and Lung Adenocarcinoma Cells.Frontiers in oncology · 2018Article
- Simvastatin-induced cell cycle arrest through inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21 accumulation in hepatocellular carcinoma cells.Cell death & disease · 2017Article
- Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells.International journal of molecular sciences · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeHigh levels of SKP2 are a poor prognostic factor in multiple human cancers and mostly correlate with low p27(KIP1) levels. Prodigiosin is a bacterial tripyrrole pigment with strong pro-apoptotic activity. Induction of cell cycle blockade underlies one of its anticancer actions but the mechanisms involved are unclear. The aim of this study was to explore the role of the SKP2-p27(KIP1) axis in prodigiosin's cytostatic effect on human lung adenocarcinoma cells. EXPERIMENTAL APPROACH: Prodigiosin's effects on cell cycle progression and long-term cell proliferation of human lung adenocarcinoma cells were characterized by flow cytometry and colony formation assay, respectively. Real-time RT-PCR and promoter activity analyses were performed for assessing transcriptional control, while cycloheximide chase analysis evaluated protein stability. Immunoblotting was employed for mechanistic study. KEY
resultsProdigiosin increased p27(KIP1) expression mainly by stabilizing p27(KIP1) through transcriptional repression of SKP2. Importantly, SKP2 overexpression or p27(KIP1) depletion restored the colony forming capacity of prodigiosin-treated cells. Furthermore, prodigiosin induced PKB dephosphorylation, leading to PKB inhibition as revealed by decreased serine 9 phosphorylation of GSK-3β. Constitutive PKB activation reduced prodigiosin-induced SKP2 repression. Prodigiosin also down-regulated E2F1 (mediates PI3K/PKB-induced SKP2 transcription), but E2F1 overexpression failed to restore SKP2 expression in prodigiosin-treated cells. CONCLUSIONS AND IMPLICATIONS: Transcriptional repression of SKP2 and the consequent accumulation of p27(KIP1) are essential for prodigiosin's antiproliferative action. Mechanistically, prodigiosin induces PKB inhibition to down-regulate SKP2 in a GSK-3β- and E2F1-independent manner. Our findings further implicate the potential for developing prodigiosin as a novel class of SKP2-targeting anticancer agent.
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