Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma.

ABSTRACT

Despite significant advances in therapy, the 5-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we show that VB significantly decreased the viability and metastasis of HN4 and HN6 tumor cells, while promoting apoptosis. A xenograft OSCC mouse model further showed that intraperitoneal injection of VB strongly inhibited growth and lung metastasis of implanted tumor cells. Immunoblot analysis confirmed that VB effectively suppressed nuclear factor (NF)-κB activation and downstream Bcl-2/Bcl-XL expression, resulting in increased OSCC cell apoptosis. In addition, VB suppressed mRNA and protein expression of matrix metalloproteinase-9 via suppression of NF-κB activation, thereby inhibiting tumor cell metastasis. Inspiringly, compared to cisplatin-treated group, VB is a biocompatible agent without signficant side effects in vivo. Collectively, our results demonstrate that VB effectively inhibits OSCC tumor cell growth and metastasis via suppression of IκB kinase complex (IKK)/NF-κB-related signaling activation, suggesting that VB has potential use as a potent anticancer agent in OSCC therapeutic strategies.