Withania somnifera root extract inhibits mammary cancer metastasis and epithelial to mesenchymal transition
Yang Z, Garcia A, Xu S, Powell DR, Vertino PM, Singh S, Marcus AI
PloS one · 48 citations
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- University or hospital
- Emory University
- University or hospital
- Winship Cancer Institute
- Government
- National Cancer Institute
- Government
- National Center for Complementary and Alternative Medicine
- Government
- National Center for Complementary and Integrative Health
- Government
- NCI NIH HHS
- Government
- NCCIH NIH HHS
- Grants
- National Cancer Institute (P30CA138292); National Center for Complementary and Integrative Health (R21 AT005231); National Center for Complementary and Integrative Health (1R21AT005231); National Cancer Institute (R01-CA077337); National Cancer Institute (3P30CA138292)
Based on 7 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2013-09-12 · PLoS One · vol. 8 · issue 9 · p. e75069
- Publisher
- Public Library of Science
- Cited
- 83 citations · more than 99% of similar papers · 19.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 69 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Phytochemicals and Medicinal Plants
- Keywords
- Withaferin A, Vimentin, Epithelial–mesenchymal transition, Withania somnifera, Metastasis, Cancer research, Cancer cell, Cancer, Cell migration, Biology, Medicine, Pathology, Cell, Internal medicine, Immunohistochemistry, Biochemistry
- MeSH
- cell line, tumor, animals, humans, mice, withania, plant roots, breast neoplasms, neoplasm metastasis, disease models, animal, transforming growth factor beta, plant extracts, antineoplastic agents, tumor burden, xenograft model antitumor assays, inhibitory concentration 50, cell movement, dose-response relationship, drug, solubility, female, epithelial-mesenchymal transition
7 authors
From US
- Zhen YangEmory University
- Anapatricia GarcíaEmory University
- Songli XuEmory University
- Doris R. PowellEmory University
- Paula M. VertinoEmory University
- Shivendra Vikram SinghUPMC Hillman Cancer Center
Abstract
Though clinicians can predict which patients are at risk for developing metastases, traditional therapies often prove ineffective and metastatic disease is the primary cause of cancer patient death; therefore, there is a need to develop anti-metastatic therapies that can be administered over long durations to specifically inhibit the motility of cancer cells. Withaniasomnifera root extracts (WRE) have anti-proliferative activity and the active component, Withaferin A, inhibits the pro-metastatic protein, vimentin. Vimentin is an intermediate filament protein and is part of the epithelial to mesenchymal transition (EMT) program to promote metastasis. Here, we determined whether WRE standardized to Withaferin A (sWRE) possesses anti-metastatic activity and whether it inhibits cancer motility via inhibition of vimentin and the EMT program. Several formulations of sWRE were created to enrich for Withaferin A and a stock solution of sWRE in EtOH could recover over 90% of the Withaferin A found in the original extract powder. This sWRE formulation inhibited breast cancer cell motility and invasion at concentrations less than 1µM while having negligible cytotoxicity at this dose. sWRE treatment disrupted vimentin morphology in cell lines, confirming its vimentin inhibitory activity. To determine if sWRE inhibited EMT, TGF-β was used to induce EMT in MCF10A human mammary epithelial cells. In this case, sWRE prevented EMT induction and inhibited 3-D spheroid invasion. These studies were taken into a human xenograft and mouse mammary carcinoma model. In both models, sWRE and Withaferin A showed dose-dependent inhibition of tumor growth and metastatic lung nodule formation with minimal systemic toxicity. Taken together, these data support the hypothesis that low concentrations of sWRE inhibit cancer metastasis potentially through EMT inhibition. Moreover, these doses of sWRE have nearly no toxicity in normal mouse organs, suggesting the potential for clinical use of orally administered WRE capsules.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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