Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways

Yubin Hao, Tianpei Xie, Alexandru Korotcov, Yanfei Zhou, Xiaowu Pang, Liang Shan, Hongguang Ji, Rajagopalan Sridhar, Paul Wang, Joseph Califano, Xinbin Gu

Research output: Contribution to journalArticle

Abstract

Overexpression of cyclooxygenase-2 (COX-2) in oral mucosa has been associated with increased risk of head and neck squamous cell carcinoma (HNSCC). Celecoxib is a nonsteroidal anti-inflammatory drug, which inhibits COX-2 but not COX-1. This selective COX-2 inhibitor holds promise as a cancer preventive agent. Concerns about cardiotoxicity of celecoxib, limits its use in long-term chemoprevention and therapy. Salvianolic acid B (Sal-B) is a leading bioactive component of Salvia miltiorrhiza Bge, which is used for treating neoplastic and chronic inflammatory diseases in China. The purpose of this study was to investigate the mechanisms by which Sal-B inhibits HNSCC growth. Sal-B was isolated from S. miltiorrhiza Bge by solvent extraction followed by 2 chromatographic steps. Pharmacological activity of Sal-B was assessed in HNSCC and other cell lines by estimating COX-2 expression, cell viability and caspase-dependent apoptosis. Sal-B inhibited growth of HNSCC JHU-022 and JHU-013 cells with IC50 of 18 and 50 lM, respectively. Nude mice with HNSCC solid tumor xenografts were treated with Sal-B (80 mg/kg/day) or celecoxib (5 mg/ kg/day) for 25 days to investigate in vivo effects of the COX-2 inhibitors. Tumor volumes in Sal-B treated group were signifi-cantly lower than those in celecoxib treated or untreated control groups (p <0.05). Sal-B inhibited COX-2 expression in cultured HNSCC cells and in HNSCC cells isolated from tumor xenografts. Sal-B also caused dose-dependent inhibition of prostaglandin E 2 synthesis, either with or without lipopolysaccharide stimulation. Taken together, Sal-B shows promise as a COX-2 targeted anticancer agent for HNSCC prevention and treatment.

Original languageEnglish (US)
Pages (from-to)2200-2209
Number of pages10
JournalInternational Journal of Cancer
Volume124
Issue number9
DOIs
StatePublished - May 1 2009

    Fingerprint

Keywords

  • Apoptosis
  • Cancer therapy
  • COX-2
  • Head and neck cancer
  • Salvianolic acid B

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Hao, Y., Xie, T., Korotcov, A., Zhou, Y., Pang, X., Shan, L., Ji, H., Sridhar, R., Wang, P., Califano, J., & Gu, X. (2009). Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivo via cyclooxygenase-2 and apoptotic pathways. International Journal of Cancer, 124(9), 2200-2209. https://doi.org/10.1002/ijc.24160