Saikosaponin-d inhibits proliferation of human undifferentiated thyroid carcinoma cells through induction of apoptosis and cell cycle arrest.

OBJECTIVE

Saikosaponin-d is a triterpene saponin derived from Bupleurum falcatum. L and has been reported to exhibit a variety of pharmacological activities such as anti-bacterial, anti-virus and anti-cancer. The aim of the present study was to explore the effect of saikosaponin-d on the proliferation and apoptosis of human undifferentiated thyroid carcinoma.

METHODS

Three human anaplastic thyroid cancers cell lines were cultured in the presence of saikosaponin-d and their proliferation was measured by MTT assay. Cell apoptosis and cell cycle distribution were analyzed with flow cytometry. Western blot was performed to determine the proteins expression. The in vivo effect of saikosaponin-d was measured with an animal model.

RESULTS

In vitro, MTT assay showed that saikosaponin-d treatment inhibited cell proliferation in three human anaplastic thyroid cancers cell lines ARO, 8305C and SW1736. In addition, saikosaponin-d promoted cell apoptosis and induced G1-phase cell cycle arrest as shown by flow cytometric analysis. On the molecular level, our results showed that saikosaponin-d treatment increased the expression of p53 and bax, and decreased the expression of Bcl-2. In addition, saikosaponin-d administration led to a significant up-regulation of p21 and down-regulation of CDK2 and cyclin D1. Xenografts tumorigenesis model demonstrated that saikosaponin-d markedly reduced the weight and volume of thyroid tumors in vivo.

CONCLUSIONS

The present study suggested that saikosaponin-d might be a new potent chemopreventive drug candidate for human undifferentiated thyroid carcinoma through induction of apoptosis and cell cycle arrest.