Journal Article

Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3

Rebecca J. Leeman-Neill, Sarah E. Wheeler, Shivendra V. Singh, Sufi M. Thomas, Raja R. Seethala, Daniel B. Neill, Mary C. Panahandeh, Eun-Ryeong Hahm, Sonali C. Joyce, Malabika Sen, Quan Cai, Maria L. Freilino, Changyou Li, Daniel E. Johnson and Jennifer R. Grandis

in Carcinogenesis

Volume 30, issue 11, pages 1848-1856
Published in print November 2009 | ISSN: 0143-3334
Published online September 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp211
Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Treatment of human head and neck squamous cell carcinoma (HNSCC) cell lines with guggulsterone, a widely available, well-tolerated nutraceutical, demonstrated dose-dependent decreases in cell viability with EC50s ranging from 5 to 8 μM. Guggulsterone induced apoptosis and cell cycle arrest, inhibited invasion and enhanced the efficacy of erlotinib, cetuximab and cisplatin in HNSCC cell lines. Guggulsterone induced decreased expression of both phosphotyrosine and total signal transducer and activator of transcription (STAT)-3, which contributed to guggulsterone's growth inhibitory effect. Hypoxia-inducible factor (HIF)-1α was also decreased in response to guggulsterone treatment. In a xenograft model of HNSCC, guggulsterone treatment resulted in increased apoptosis and decreased expression of STAT3. In vivo treatment with a guggulsterone-containing natural product, Guggulipid, resulted in decreased rates of tumor growth and enhancement of cetuximab's activity. Our results suggest that guggulsterone-mediated inhibition of STAT3 and HIF-1α provide a biologic rationale for further clinical investigation of this compound in the treatment of HNSCC.

Journal Article.  6091 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.