ArticleScientific reports2017
Concomitant activation of ETS-like transcription factor-1 and Death Receptor-5 via extracellular signal-regulated kinase in withaferin A-mediated inhibition of hepatocarcinogenesis in mice.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
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- Targeting RSK2 in Cancer Therapy: A Review of Natural Products.Anti-cancer agents in medicinal chemistry · 2025Review
- A Review on Nanotechnologically Derived Phytomedicines for the Treatment of Hepatocellular Carcinoma: Recent Advances in Molecular Mechanism and Drug Targeting.Current drug targets · 2025Review
- Biopolymeric nanocarriers in cancer therapy: unleashing the potency of bioactive anticancer compounds for enhancing drug delivery.RSC advances · 2024Review
- The Therapeutic Effects of Withaferin A against Cancer: Overview and Updates.Current molecular medicine · 2024Review
- Phytocompounds targeting epigenetic modulations: an assessment in cancer.Frontiers in pharmacology · 2023Review
- 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
- Metformin Enhances the Anti-Cancer Efficacy of Sorafenib via Suppressing MAPK/ERK/Stat3 Axis in Hepatocellular Carcinoma.International journal of molecular sciences · 2022Article
- Withaferin A in the Treatment of Liver Diseases: Progress and Pharmacokinetic Insights.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Computational Identification of BCR-ABL Oncogenic Signaling as a Candidate Target of Withaferin A and Withanone.Biomolecules · 2022Article
- Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis.Frontiers in veterinary science · 2022Article
- Tackling Chronic Inflammation with Withanolide Phytochemicals-A Withaferin a Perspective.Antioxidants (Basel, Switzerland) · 2020Review
- Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer, Part 2: A Review on Cytotoxic, Antiproliferative, and Antitumor Phytochemicals, and Future Perspective.Molecules (Basel, Switzerland) · 2020Review
- Genetic variation in NRG 1 gene and risk of post-traumatic stress disorders in patients with hepatocellular carcinoma.Journal of clinical laboratory analysis · 2020Article
- SRC-1 and Twist1 are prognostic indicators of liver cancer and are associated with cell viability, invasion, migration and epithelial-mesenchymal transformation of hepatocellular carcinoma cells.Translational cancer research · 2020Article
- The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight.Frontiers in oncology · 2020Review
- Concomitant Inhibition of Cytoprotective Autophagy Augments the Efficacy of Withaferin A in Hepatocellular Carcinoma.Cancers · 2019Article
- Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) has the second lowest 5-year survival rate (~16%) of all tumor types partly owing to the lack of effective therapeutic agents. Withaferin A (WA) is a bioactive molecule derived from Withania somnifera and the present study is designed to systemically investigate the anti-HCC efficacy of WA. WA inhibited growth, migration and invasion of HCC cells. Using a phospho-kinase screening array, we discovered that WA increased phosphorylation of ERK and p38 in HCC. Further analyses revealed a key role of ERK leading to increased phosphorylation of p90-ribosomal S6 kinase (RSK) and a concomitant activation of ETS-like transcription factor-1(ELK1) and Death Receptor protein-5 (DR5) in HCC. Importantly, oral administration of WA effectively inhibited HepG2-xenografts and DEN-induced-HCC in C57BL/6 mice. Analyses of WA-treated HepG2-xenografts and DEN-induced-HCC tumors showed elevated levels of ERK, RSK, ELK1 and DR5 along with decreased expression of Ki67. In silico analyses of HCC, utilizing published profiling studies showed an inverse correlation between DR5 and Ki67. These data showed the efficacy of WA as an effective agent for HCC inhibition and provided first in vitro and in vivo evidence supporting the key role of a novel crosstalk between WA, ERK/RSK, ELK1, and DR5 in HCC inhibition.
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