Small Molecule Therapeutics Lappaol F, a Novel Anticancer Agent Isolated from Plant Arctium Lappa L

In an effort to search for new cancer-fighting therapeutics, we identified a novel anticancer constituent, Lappaol F, fromplantArctiumLappaL. Lappaol F suppressed cancer cell growth in a timeanddose-dependent manner inhumancancer cell lines of various tissue types.We found thatLappaol F inducedG1 andG2 cell-cycle arrest, which was associated with strong induction of p21 and p27 and reduction of cyclin B1 and cyclindependent kinase 1 (CDK1). Depletion of p21 via genetic knockout or short hairpin RNA (shRNA) approaches significantly abrogated Lappaol F–mediated G2 arrest and CDK1 and cyclin B1 suppression. These results suggest that p21 seems to play a crucial role in Lappaol F–mediated regulation of CDK1 and cyclin B1 and G2 arrest. Lappaol F–mediated p21 induction was found to occur at the mRNA level and involved p21 promoter activation. Lappaol Fwas also found to induce cell death in several cancer cell lines and to activate caspases. In contrast with its strong growth inhibitory effects on tumor cells, Lappaol F had minimal cytotoxic effects on nontumorigenic epithelial cells tested. Importantly, our data also demonstrate that Lappaol F exhibited strong growth inhibition of xenograft tumors in nude mice. Lappaol F was well tolerated in treated animals without significant toxicity. Taken together, our results, for thefirst time, demonstrate that Lappaol F exhibits antitumor activity in vitro and in vivo and has strong potential to be developed as an anticancer therapeutic. Mol Cancer Ther; 13(1); 49–59. 2013 AACR.