title: Total alkaloids of Rubus aleaefolius Poir. inhibit the STAT3 signaling pathway leading to suppression of proliferation and cell cycle arrest in a mouse model of hepatocellular carcinoma.
abstract: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in cell survival and proliferation and is constitutively activated in many types of human cancers including hepatocellular carcinoma (HCC). Therefore, it is a major focus in the development of anticancer agents. Rubus aleaefolius Poir. has been demonstrated to be effective in the treatment of HCC. However, the precise mechanism of its anticancer activity remains largely unknown. Using HepG2 cells and a HCC mouse xenograft model, in the present study we evaluated the effect of the total alkaloids of Rubus aleaefolius Poir. (TARAP) on tumor growth in vitro and in vivo and investigated the underlying molecular mechanisms. We found that TARAP inhibited the proliferation of HepG2 human HCC cells and blocked G1/S cell cycle progression. In addition, TARAP treatment suppressed STAT3 phosphorylation in tumor tissues. Consequently, the inhibitory effect of TARAP on STAT3 activation resulted in the inhibition of proliferation. Moreover, TARAP altered the expression of several important target genes of the STAT3 signaling pathway, such as decreased expression of cyclinD1, cyclinE, cyclin-dependent kinase (CDK) 4 and CDK2 as well as upregulated p21. These results suggest that suppression of the STAT3 signaling pathway leading to inhibition of proliferation and cell cycle arrest may be one of the mechanisms of the anticancer activity of TARAP against HCC.
authors.affiliation: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Cao
authors.forename: Liya
authors.initials: L
authors.lastname: Liu
authors.forename: Qunchuan
authors.initials: Q
authors.lastname: Zhuang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhong
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Hong
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027824:Rosaceae / Q000737:chemistry*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000470:Alkaloids; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor