Beijing Solarbio Science & Technology Co., Ltd. [China]

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We studied the mechanism of anti-tumor activity of the flavonoid Casticin, derived from Achillea millefolium. Casticin anti-tumor activity results in cell growth arrest in G2/M and in apoptotic death. As a tubulin-binding agent (TBA), Casticin induces p21, which in turn inhibits Cdk1. Moreover, Casticin appears to down regulate cyclin A. These observations could explain Casticin-induced G2/M arrest. Following Casticin exposure, Bcl-2 depletion occurs in cancer cells, and a sub-G1 accumulation occurs in the cell cycle. Moreover, following a transient transfection with Bcl-2, MN1 cells are resistant to Casticin. A number of features suggest that Casticin could be important in cancer therapy. Indeed, Pgp over expressing cells are not resistant to Casticin, and its cell killing effect is observed even in p53 mutant or null cell lines.