Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

25 January 2018 : Laboratory Research  

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: Anti-Inflammatory Agents, Cyclooxygenase 2, herbal medicine, NF-kappa B, Nitric Oxide Synthase Type II

0 Comments

Editorial

01 December 2021 : Editorial  

Editorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19

Dinah V. Parums
Scientific Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.935624

Med Sci Monit 2021; 27:e935624

SARS-CoV-2/COVID-19

03 December 2021 : Laboratory Research  

Influenza and Influenza-Like Respiratory Virus Infections in Children During the 2019/20 Influenza Season a...

Med Sci Monit In Press; DOI: 10.12659/MSM.934862  

08 November 2021 : Database Analysis  

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Cor...

Med Sci Monit In Press; DOI: 10.12659/MSM.934102  

01 December 2021 : Editorial  

Editorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19

Med Sci Monit 2021; 27:e935624

In Press

06 Dec 2021 : Animal Research  

Astragalus Flavone Induces Proliferation and Differentiation of Neural Stem Cells in a Cerebral Infarction ...

Med Sci Monit In Press; DOI: 10.12659/MSM.933830  

06 Dec 2021 : Clinical Research  

Alteration of Serum Metabolites in Women of Reproductive Age with Chronic Constipation

Med Sci Monit In Press; DOI: 10.12659/MSM.934117  

06 Dec 2021 : Clinical Research  

Body Composition Changes and Related Factors in Patients with Ulcerative Colitis: A Retrospective Single-Ce...

Med Sci Monit In Press; DOI: 10.12659/MSM.933942  

03 Dec 2021 : Clinical Research  

A Retrospective Single-Center Study of 23 Patients to Compare Gait Before and After Total Hip Arthroplasty ...

Med Sci Monit In Press; DOI: 10.12659/MSM.934558  

Most Viewed Current Articles

20 Mar 2020 : Clinical Research  

Social Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Diseas...

DOI :10.12659/MSM.923921

Med Sci Monit 2020; 26:e923921

15 Apr 2020 : Clinical Research  

Psychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...

DOI :10.12659/MSM.924171

Med Sci Monit 2020; 26:e924171

05 May 2020 : Review article  

An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development

DOI :10.12659/MSM.924700

Med Sci Monit 2020; 26:e924700

26 Apr 2020 : Clinical Research  

Comparison of Prevalence and Associated Factors of Anxiety and Depression Among People Affected by versus P...

DOI :10.12659/MSM.924609

Med Sci Monit 2020; 26:e924609

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750