title: Total alkaloids of Rubus alceifolius Poir inhibit tumor angiogenesis through suppression of the Notch signaling pathway in a mouse model of hepatocellular carcinoma.
abstract: Angiogenesis, which has a critical role in human tumor growth and development, is tightly regulated by the Notch signaling pathway. Total alkaloids are active components of the plant Rubus alceifolius Poir, which is used for the treatment of various types of cancer. A previous study by our group showed that the total alkaloids of Rubus alceifolius Poir (TARAP) induced hepatocellular carcinoma (HCC) cell apoptosis through the activation of the mitochondria-dependent pathway in vitro and in vivo, as well as inhibited angiogenesis in a chick embryo chorioallantoic membrane model. In the present study, to further analyze the specific mechanisms underlying the antitumor activity of TARAP, a HCC xenograft mouse model was used to assess the effect of TARAP on angiogenesis in vivo. TARAP was found to suppress the expression of vascular endothelial growth factor (VEGF) A and VEGF receptor-2 in tumor tissues, which resulted in the inhibition of tumor angiogenesis. In addition, TARAP treatment was observed to inhibit the expression of Notch1, delta-like ligand 4 and jagged 1, which are key mediators of the Notch signaling pathway. The present study identified that the inhibition of tumor angiogenesis through the suppression of the Notch signaling pathway may be one of the mechanisms through which TARAP may be effective in the treatment of cancer.
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Qunchuan
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Liangpu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Hong
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D065856:Rubus / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000470:Alkaloids; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2