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, Jennifer R. Grandis

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1848-1856
Number of pages9
JournalCarcinogenesis
Volume30
Issue number11
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Cancer Research

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    Leeman-Neill, R. J., Wheeler, S. E., Singh, S. V., Thomas, S. M., Seethala, R. R., Neill, D. B., Panahandeh, M. C., Hahm, E. R., Joyce, S. C., Sen, M., Cai, Q., Freilino, M. L., Li, C., Johnson, D. E., & Grandis, J. R. (2009). Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis, 30(11), 1848-1856. https://doi.org/10.1093/carcin/bgp211