ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2012
Natural withanolide withaferin A induces apoptosis in uveal melanoma cells by suppression of Akt and c-MET activation.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- High c-Met expression is a negative prognostic marker for colorectal cancer: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Pooled it
- Uveal Melanoma Zebrafish Xenograft Models Illustrate the Mutation Status-Dependent Effect of Compound Synergism or Antagonism.Investigative ophthalmology & visual science · 2024Article
- Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.Drug design, development and therapy · 2023Review
- Review
- Withaferin A: From Ancient Remedy to Potential Drug Candidate.Molecules (Basel, Switzerland) · 2021Review
- Withaferin A-A Promising Phytochemical Compound with Multiple Results in Dermatological Diseases.Molecules (Basel, Switzerland) · 2021Review
- Autophagy-Related Long Non-coding RNA Signature as Indicators for the Prognosis of Uveal Melanoma.Frontiers in genetics · 2021Article
- Withaferin A activates TRIM16 for its anti-cancer activity in melanoma.Scientific reports · 2020Article
- Mouse models of uveal melanoma: Strengths, weaknesses, and future directions.Pigment cell & melanoma research · 2020Review
- Broad-spectrum antitumor properties of Withaferin A: a proteomic perspective.RSC medicinal chemistry · 2020Review
- Plant-Based Scaffolds Modify Cellular Response to Drug and Radiation Exposure Compared to Standard Cell Culture Models.Frontiers in bioengineering and biotechnology · 2020Article
- Article
- Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice.Pharmaceutical biology · 2017Article
- Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M cell cycle arrest and apoptosis.Oncology letters · 2017Article
- Article
- WITHAFERIN A INDUCES APOPTOSIS IN RAT C6 GLIOMA CELLS THROUGH REGULATING NF-KB NUCLEAR TRANSLOCATION AND ACTIVATION OF CASPASE CASCADE.African journal of traditional, complementary, and alternative medicines : AJTCAM · 2017Article
- Withaferin-A--A Natural Anticancer Agent with Pleitropic Mechanisms of Action.International journal of molecular sciences · 2016Review
- Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling.Oncotarget · 2016Article
- Recent Advances in the Development of Antineoplastic Agents Derived from Natural Products.Drugs · 2015Review
- Regulation of MET-mediated proliferation of thyroid carcinoma cells by miR-449b.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. While effective therapy exists for the primary tumor, there is a lack of effective treatment for metastatic disease currently. Natural withanolide withaferin A (WA) has shown efficacy in cancers demonstrating upregulation of pro-survival pathways. The purpose of the present study is to investigate the effect of WA as a potential therapeutic agent for UM in vitro as well as in vivo. UM cells were treated with WA and several cell-based assays, such as MTS, trypan blue exclusion assay, clonogenic, wound healing, cell cycle shift, annexin V/propidium iodide, and Western blot, were performed. In vivo experiments utilized the 92.1 cells in a xenograft murine model. WA inhibits cell proliferation of uveal melanoma cells with an IC50 of 0.90, 1.66, and 2.42 μM for OMM2.3, 92.1, and MEL290 cells, respectively. Flow cytometry analysis demonstrates G2/M cell cycle arrest and apoptosis at 1 μM WA in treated cells. WA induced apoptosis partly through the suppression of c-Met, Akt, and Raf-1 signaling activation. In vivo studies using WA reduced tumor growth in 100% of animals (p = 0.015). Our observation indicates that WA is a potent drug that inhibits cell proliferation, shifts cell cycle arrest, and induces apoptosis in multiple UM cell lines in vitro. WA-mediated apoptosis in UM cells is partly mediated though the suppression of c-Met and Akt activation. WA significantly decreases UM tumor growth in vivo and justifies further evaluation of this drug for the treatment of metastatic uveal melanoma.
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Registered trials
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