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 citas
Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Universidad u hospital
- Emory University
- Universidad u hospital
- Winship Cancer Institute
- Gobierno
- National Cancer Institute
- Gobierno
- National Center for Complementary and Alternative Medicine
- Gobierno
- National Center for Complementary and Integrative Health
- Gobierno
- NCI NIH HHS
- Gobierno
- NCCIH NIH HHS
- Subvenciones
- 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)
Según 7 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2013-09-12 · PLoS One · vol. 8 · número 9 · pág. e75069
- Editorial
- Public Library of Science
- Citado
- 83 citas · más que el 99% de estudios similares · 19.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 69 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Phytochemicals and Medicinal Plants
- Palabras clave
- 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 autores
- Zhen Yang🇺🇸Emory University
- Anapatricia García🇺🇸Emory University
- Songli Xu🇺🇸Emory University
- Doris R. Powell🇺🇸Emory University
- Paula M. Vertino🇺🇸Emory University
- Shivendra Vikram Singh🇺🇸UPMC Hillman Cancer Center
- Adam I. Marcus🇺🇸 · autor de correspondenciaEmory University
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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