title: A small-molecule induces apoptosis and suppresses metastasis in pancreatic cancer cells.
abstract: Pancreatic cancer is one of the most malignant tumor diseases with the characters of aggressive growth and metastasis. With the inefficiency of the current therapeutics, new potential targets and new therapeutic agents for healing of pancreatic cancer are critically needed. We have previously found a small molecule, named 4-tert-butyl-2-[(cyclohexylamino) methyl]-6-methylphenol (TBMMP, NSC number: 48160), which can freeze the intermediate of Ras-GTP hydrolysis in the open non-signaling conformation with high affinity and high specificity in silico. In this work, we studied the effect and mechanism of TBMMP on two pancreatic cancer cell lines, CFPAC-1 and BxPC-3. The results showed that TBMMP could restrain the growth of the pancreatic cancer cells with IC(50) value 84.3 μM for CPFAC-1 and 94.5 μM for BxPC-3, respectively. Additionally, TBMMP increased cytochrome c release, reduced mitochondrial membrane potential, activated caspase-3, -9, elevated ROS and increased expression of the Bax in the pancreatic cancer cell lines. The results indicated that TBMMP induced the apoptosis of pancreatic cancer cells through the mitochondrial pathway. Further, we also found that TBMMP could suppress the metastasis of both pancreatic cancer cells in vitro. Taken together, we proposed that TBMMP might be a therapeutic potential lead for treating patients with pancreatic cancer.
authors: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.
authors: Dan
authors: D
authors: Li
authors: Zuojia
authors: Z
authors: Liu
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 / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003514:Cyclohexylamines / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014945:Wound Healing; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C583083:4-tert-butyl-2-((cyclohexylamino)methyl)-6-methylphenol; D000970:Antineoplastic Agents; C494826:BAX protein, human; D001596:Benzylamines; D003514:Cyclohexylamines; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c