25 January 2018 : Laboratory Research
[Retracted: 31 Dec 2024] Ingenol-3-Angelate Suppresses Growth of Melanoma Cells and Skin Tumor Development by Downregulation of NF-κB-Cox2 Signaling
Dunwei Wang1ABCDF, Pengcheng Liu2ABCDEFG*DOI: 10.12659/MSM.906049
Med Sci Monit 2018; 24: MOL486-502
Abstract
BACKGROUND: A recent focus in skin cancer prevention intervenes though modulating molecular links between inflammation and cell growth signaling, such as NF-κB. This study elucidates the effect of a non-tumor promoting phorbol ester, ingenol-3-angelate (I3A), on the growth of human melanoma cells and on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation and 7,12-Dimethylbenz(a)anthracene (DMBA)-induced skin carcinoma in mice.
MATERIAL AND METHODS: Cell viability was assessed by MTT assay, cell proliferation by clonogenic assay, apoptosis and cell cycle arrest was analyzed by flow cytometry, protein expression was studied by IHC and Western blotting, and gene expression by qPCR.
RESULTS: I3A suppressed the survival and proliferation of human melanoma cells with estimated IC50 values around 38 and 46 μM for A2058 and HT144 cell, respectively. I3A activated the protein levels of PKCδ and PKCε, which induced apoptosis by activating caspase-9 and caspace-3 followed by lowering of mitochondrial membrane potential and enhancing DNA fragmentation. I3A induced G1 phase cell cycle arrest as well as G2/M phase arrest in both cell lines. I3A inhibited the levels of NFκB p65 protein as well as phosphorylation of p65 and its nuclear translocation. I3A suppressed the gene expression of NF-κB, COX-2 and iNOS. I3A inhibited TPA-induced inflammation and epidermal hyperplasia in female ICR mice by downregulating NF-κB and iNOS. I3A suppressed the growth of skin tumor in DMBA-induced mice in dose-dependent manner.
CONCLUSIONS: The mechanism of I3A induces apoptosis in human melanoma cells and suppresses skin inflammation and carcinoma via downregulation of NF-κB-iNOS-COX-2 signaling.
Keywords: Retracted Publication
Retraction note
- Download PDF
- Order reprints
- Export Article
- Related articles
- Share by email
- Metrics
1,808 13
Editorial
01 February 2025 : Editorial
Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-SmokersDOI: 10.12659/MSM.948255
Med Sci Monit 2025; 31:e948255
In Press
Review article
Hydrogels in Oral Disease Management: A Review of Innovations in Drug Delivery and Tissue RegenerationMed Sci Monit In Press; DOI: 10.12659/MSM.946122
Clinical Research
Procedure Dynamics in Transfemoral vs Transradial Cerebral Angiography: A Retrospective StudyMed Sci Monit In Press; DOI: 10.12659/MSM.947603
Clinical Research
Predicting Cerebral Small Vessel Disease Burden Based on Thromboelastography in Patients with Acute Ischemi...Med Sci Monit In Press; DOI: 10.12659/MSM.946303
Clinical Research
Long-Term Outcomes of Implanon in Managing Adenomyosis: A 3-Year Prospective StudyMed Sci Monit In Press; DOI: 10.12659/MSM.945972
Most Viewed Current Articles
17 Jan 2024 : Review article 6,969,459
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research 701,879
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Mar 2024 : Editorial 25,628
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...DOI :10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
28 Jan 2024 : Review article 20,173
A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and FutureDOI :10.12659/MSM.943912
Med Sci Monit 2024; 30:e943912