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, 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.
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.
Qing
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Kanglun
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Liu
Xiaoling
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Shen
Weixin
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Jin
Lingyan
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Jiang
M Saeed
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Yingjie
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D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D031170:Arctium / Q000737:chemistry; D001572:Benzofurans / Q000008:administration & dosage*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001572:Benzofurans; D010936:Plant Extracts; C000591899:lappaol F; D015107:4-Butyrolactone