Salvianolic acid B inhibits growth of head and neck squamous cell carcinoma in vitro and in vivovia cyclooxygenase‐2 and apoptotic pathways

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 μM, 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 significantly 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 E2 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. © 2008 Wiley‐Liss, Inc.

Rosmarinic acid and its derivatives: biotechnology and applications

“…Salvianolic acid B also shows promise as a cyclooxygenase 2-targeted anticancer agent for the prevention and treatment of head and neck squamous-cell carcinoma (Hao et al, 2009).…”

Salvianolic Acid B, a Potential Chemopreventive Agent, for Head and Neck Squamous Cell Cancer

“…Mounting studies have reported that Sal-B is capable of preventing the development of cancer; and the possible antiinflammatory mechanisms of Sal-B involve modulating cytokines, Cyclooxygenase-2/prostaglandin E2 (COX-2/PGE-2) pathway [24, 25, 29], NF- κ B [30–32], TNF- α [33–35] and MMPs [36–38]. Numbers of clinical experiences indicate its effectiveness and safety in contrast to the disadvantages of nonsteroidal antiinflammatory drugs (NSAIDs).…”

Effect of Salvianolic Acid B on Cardiac Muscle Damage Following Exhaustive Exercise in Rats

“…Salvianolic acid는 수용성으 로 salvianolic acid A (SAA)와 salvianolic acid B (SAB)로 구분되며 간 보호효능 2) , 신경손상 보호효능 3) , 항암 효능 4) 등이 있는 것으로 보고되어 있다. SAA와 SAB 모두 높은 항 산화 작용이 있는 것으로 보고되고 있으며 5) , 특히 SAB는 혈관내피세포, 혈관 평활근세포 및 심근세포에 대한 연구들 을 통해 심혈관 보호(cardiovascular protection)와 심장손 상 보호(cardioprotection)의 효능이 있다고 하였다 6) .…”