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: Noriyuki Takai, Naoko Kira, Terukazu Ishii, Toshie Yoshida, Masakazu Nishida, Yoshihiro Nishida, Kaei Nasu, Masayuki Takano, Haruna Midori, Satoko Koga, Hisashi Narahara
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 33 Issue 5 Pg. 1505-10 (Oct 2012) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 22528948 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Cell Cycle Proteins
• Isoquinolines
• Ligands
• Receptors, GABA
• TSPO protein, human
• Caspase 3
• Caspase 7
• PK 11195

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Caspase 3 (metabolism)
• Caspase 7 (metabolism)
• Cell Cycle (drug effects)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Enzyme Activation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hydatidiform Mole, Invasive (genetics, metabolism)
• Isoquinolines (pharmacology)
• Ligands
• Membrane Potential, Mitochondrial (drug effects)
• Pregnancy
• Receptors, GABA (metabolism)
• Uterine Neoplasms (genetics, metabolism)