title: Antiproliferative and antimetastatic effects of emodin on human pancreatic cancer.
abstract: Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is an active constituent isolated from the root of Rheum palmatum L and is the main effective component of some Chinese herbs and plants. Pharmacological studies have demonstrated that emodin exhibits anti-cancer effects on several human cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. This study was performed to investigate the antiproliferative and antimetastatic effects of emodin on pancreatic cancer in vitro and in vivo. Our results showed that emodin induced a higher percentage of growth inhibition and apoptosis in the pancreatic cancer cell line SW1990 compared to that of control, and emodin suppressed the migration and invasion of SW1990 cells in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and Western blot analysis, and found that emodin significantly down-regulated NF-κB DNA-binding activity, survivin and MMP-9 in SW1990 cells. Moreover, the expression of cleaved caspase-3 was up-regulated in SW1990 cells after treatment with emodin. In addition, a metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into the pancreatic wall of nude mice. Oral administration of emodin significantly decreased tumor weight and metastasis compared to control. Furthermore, the expression of NF-κB, survivin and MMP-9 were also suppressed in tumor tissues after treatment with emodin. Collectively, our results indicated that emodin exerts antiproliferative and antimetastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-κB and its regulated molecules such as survivin and MMP-9 proteins. Consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human pancreatic cancer.
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical College, No. 109, West Xue-yuan Road, Wenzhou 325027, PR China.
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Weitian
authors.initials: W
authors.lastname: Wei
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.forename: Jianming
authors.initials: J
authors.lastname: Gong
authors.forename: Zhengcai
authors.initials: Z
authors.lastname: Jiang
authors.forename: Lian
authors.initials: L
authors.lastname: Wang
authors.forename: Shengzhang
authors.initials: S
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D000077022:Survivin; D020780:Matrix Metalloproteinase 9; D004642:Emodin