title: A potent lead induces apoptosis in pancreatic cancer cells.
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 IC(50) value of 12.9±0.2, 20.6±0.3, and 6.2±0.6 µM 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 lines. From this perspective, NSC48693 should help to open up a new opportunity for the treatment of patients with pancreatic cancer.
authors: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.
authors: Zuojia
authors: Z
authors: Liu
authors: Dan
authors: D
authors: Li
authors: Wenjing
authors: W
authors: Zhao
authors: Xiliang
authors: X
authors: Zheng
authors: Jin
authors: J
authors: Wang
authors: Erkang
authors: E
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c