Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells

Wenjing Zhao; Dan Li; Zuojia Liu; Xiliang Zheng; Jin Wang; Erkang Wang

doi:10.1371/journal.pone.0066362

Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells

PLoS One. 2013 Jun 20;8(6):e66362. doi: 10.1371/journal.pone.0066362. Print 2013.

Authors

Wenjing Zhao¹, Dan Li, Zuojia Liu, Xiliang Zheng, Jin Wang, Erkang Wang

Affiliation

¹ State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Adhesion
Cell Line, Tumor / drug effects
Cell Movement / drug effects*
Cell Survival / drug effects*
Drug Screening Assays, Antitumor
HEK293 Cells
Humans
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Membrane Potential, Mitochondrial / drug effects
Neoplasm Invasiveness
Pancreatic Neoplasms / drug therapy*
Pancreatic Neoplasms / pathology
Phenothiazines / pharmacology*
Reactive Oxygen Species / metabolism
Spiro Compounds / pharmacology*

Substances

8-(3-(2-chloro-10H-phenothiazin-10-yl)propyl)-1-thia-4,8-diazaspiro(4.5)decan-3-one
Antineoplastic Agents
Phenothiazines
Reactive Oxygen Species
Spiro Compounds
MMP2 protein, human
Matrix Metalloproteinase 2
MMP9 protein, human
Matrix Metalloproteinase 9

Grants and funding

The work was funded by the following: National Natural Science Foundation of China (11174105, 21190040); 973 Project (2009CB930100, 2010CB933600). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.