title: Sedum sarmentosum Bunge extract induces apoptosis and inhibits proliferation in pancreatic cancer cells via the hedgehog signaling pathway.
abstract: Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide range of clinical applications including antibiosis, anti-inflammation and anti-oxidation. In the present study, we identified that its extract (SSBE) exerts pancreatic anticancer activity in vitro and in vivo. In the cultured pancreatic cancer PANC-1 cell line, SSBE inhibited cell growth in a concentration-dependent manner, and it was accompanied by the downregulated expression of proliferating cell nuclear antigen (PCNA). In addition, SSBE treatment also increased cellular apoptosis in a mitochondrial-dependent manner. Moreover, SSBE induced p53 expression, reduced c-Myc expression, and inhibited epithelial-mesenchymal transition (EMT). The antiproliferative activity of SSBE in the pancreatic cancer cells was found to be closely related to cell cycle arrest at the G2/M phase by upregulating p21(Waf1/CIP1) expression. Further study showed that this inhibitory effect of SSBE was through downregulation of the activity of the proliferation-related Hedgehog signaling pathway. Exogenous recombinant protein Shh was used to activate Hedgehog signaling, thereby resulting in the abolishment of the SSBE-mediated inhibition of pancreatic cancer cell growth. In animal xenograft models of pancreatic cancer, activated Hedgehog signaling was also observed compared with the vehicle controls, but was reduced by SSBE administration. As a result, SSBE suppressed the growth of pancreatic tumors. Thus, these findings demonstrate that SSBE has therapeutic potential for pancreatic cancer, and this anticancer effect in pancreatic cancer cells is associated with inhibition of the Hedgehog signaling pathway.
authors.affiliation: Key Laboratory of Clinical Laboratory Diagnostics, Ministry of Education, College of Clinical Laboratory Diagnostics, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Chen
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Hong
authors.affiliation: Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Clinical Laboratory Diagnostics, Ministry of Education, College of Clinical Laboratory Diagnostics, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D031963:Sedum / Q000737:chemistry; D015398:Signal Transduction; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053823:Hedgehog Proteins; D010936:Plant Extracts