title: Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells.
abstract: The effective treatment for pancreatic carcinoma remains critically needed. Herein, this current study showed that spiclomazine treatment caused a reduction in viability in pancreatic carcinoma cell lines CFPAC-1 and MIA PaCa-2 in vitro. It was notable in this regard that, compared with pancreatic carcinoma cells, normal human embryonic kidney (HEK-293) and liver (HL-7702) cells were more resistant to the antigrowth effect of spiclomazine. Biochemically, spiclomazine treatment regulated the expression of protein levels in the apoptosis related pathways. Consistent with this effect, spiclomazine reduced the mitochondria membrane potential, elevated reactive oxygen species, and activated caspase-3/9. In addition, a key finding from this study was that spiclomazine suppressed migration and invasion of cancer cells through down-regulation of MMP-2/9. Collectively, the proposed studies did shed light on the antiproliferation effect of spiclomazine on pancreatic carcinoma cell lines, and further clarified the mechanisms that spiclomazine induced apoptosis associated with the suppression of migration and invasion.
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Zuojia
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zheng
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Erkang
authors.initials: E
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010640:Phenothiazines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: C586072:8-(3-(2-chloro-10H-phenothiazin-10-yl)propyl)-1-thia-4,8-diazaspiro(4.5)decan-3-one; D000970:Antineoplastic Agents; D010640:Phenothiazines; D017382:Reactive Oxygen Species; D013141:Spiro Compounds; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9