1. Academic Validation
  2. Lappaol F, a novel anticancer agent isolated from plant arctium Lappa L

Lappaol F, a novel anticancer agent isolated from plant arctium Lappa L

  • Mol Cancer Ther. 2014 Jan;13(1):49-59. doi: 10.1158/1535-7163.MCT-13-0552.
Qing Sun 1 Kanglun Liu Xiaoling Shen Weixin Jin Lingyan Jiang M Saeed Sheikh Yingjie Hu Ying Huang
Affiliations

Affiliation

  • 1 Corresponding Authors: Ying Huang, Department of Pharmacology, State University of New York, Upstate Medical University 750 East Adams Street, Syracuse, NY 13210. huangy@upstate.edu.
Abstract

In an effort to search for new cancer-fighting therapeutics, we identified a novel Anticancer constituent, Lappaol F, from plant Arctium Lappa L. Lappaol F suppressed Cancer cell growth in a time- and dose-dependent manner in human Cancer cell lines of various tissue types. We found that Lappaol F induced G(1) and G(2) cell-cycle arrest, which was associated with strong induction of p21 and p27 and reduction of cyclin B1 and cyclin-dependent kinase 1 (CDK1). Depletion of p21 via genetic knockout or short hairpin RNA (shRNA) approaches significantly abrogated Lappaol F-mediated G(2) 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 G(2) arrest. Lappaol F-mediated p21 induction was found to occur at the mRNA level and involved p21 promoter activation. Lappaol F was 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 the first time, demonstrate that Lappaol F exhibits antitumor activity in vitro and in vivo and has strong potential to be developed as an Anticancer therapeutic.

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