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a potent lead induces apoptosis in pancreatic cancer cells一个强有力的领导在胰腺癌细胞凋亡
A Potent Lead Induces Apoptosis in Pancreatic Cancer
Cells
1. 1. 1 1 1,2 1
Zuojia Liu , Dan Li , Wenjing Zhao , Xiliang Zheng , Jin Wang *, Erkang Wang *
1 State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China, 2 Department of
Chemistry and Physics, State University of New York, Stony Brook, New York, United States of America
Abstract
Pancreatic cancer is considered a lethal and treatment-refractory disease. To obtain a potent anticancer drug, the cytotoxic
effect of 2-(benzo[d]oxazol-3(2H)-ylmethyl)- 5-((cyclohexylamino)methyl)benzene-1,4-diol, dihydrochloride (NSC48693) on
human pancreatic cancer cells CFPAC-1, MiaPaCa-2, and BxPC-3 was assessed in vitro. The proliferation of CFPAC-1,
MiaPaCa-2, and BxPC-3 is inhibited with IC50 value of 12.9 60.2, 20.6 60.3, and 6.2 60.6 mM at 48 h, respectively. This
discovery is followed with additional analysis to demonstrate that NSC48693 inhibition is due to induction of apoptosis,
including Annexin V staining, chromatins staining, and colony forming assays. It is further revealed that NSC48693 induces
the release of cytochrome c, reduces mitochondrial membrane potential, generates reactive oxygen species, and activates
caspase. These results collectively indicate that NSC48693 mainly induces apoptosis of CFPAC-1, MiaPaCa-2, and BxPC-3 cells
by the mitochondrial-mediated apoptotic pathway. Excitingly, the study highlights an encouraging inhibition effect that
human embryonic kidney (HEK-293) and liver (HL-7702) cells are more resistant to the antigrowth effect of NSC48693
compared to the three cancer cell line
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