title: A translocator protein ligand PK11195 shows antigrowth activity in human choriocarcinoma cells.
abstract: The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein ligand (initially described as a ligand for the peripheral benzodiazepine receptor), induces apoptosis in some lines of human tumor cells. We investigated the effect of PK11195 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of PK11195, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of PK11195. In contrast, the nonsite selective ligand diazepam has a little effect on these cells. Cell cycle analysis indicated that exposure to PK11195 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that PK11195 may serve as a therapeutic agent for the treatment of choriocarcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan. takai@oita-u.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takai
authors.forename: Naoko
authors.initials: N
authors.lastname: Kira
authors.forename: Terukazu
authors.initials: T
authors.lastname: Ishii
authors.forename: Toshie
authors.initials: T
authors.lastname: Yoshida
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nishida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishida
authors.forename: Kaei
authors.initials: K
authors.lastname: Nasu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takano
authors.forename: Haruna
authors.initials: H
authors.lastname: Midori
authors.forename: Satoko
authors.initials: S
authors.lastname: Koga
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narahara
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D002820:Hydatidiform Mole, Invasive / Q000235:genetics / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*; D008024:Ligands; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011247:Pregnancy; D018079:Receptors, GABA / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D007546:Isoquinolines; D008024:Ligands; D018079:Receptors, GABA; C499229:TSPO protein, human; D053148:Caspase 3; D053179:Caspase 7; C037850:PK 11195