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Research Paper
Furanonaphthoquinones Cause Apoptosis of Cancer Cells by Inducing the Production of Reactive Oxygen Species by the Mitochondrial Voltage-dependent Anion Channel
Kei-Ichi Hirai, Hiroki Shimada, Junko Koyama, Yukie Niwa and Shigeomi Shimizu
volume 5 | issue 11
November 2006Pages: 1523 - 1529
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The mitochondrial production of reactive oxygen species (ROS) has been implicated in the anticancer activity of furanonaphthoquinone. However, the mechanism of the activation remains elusive. In the current study, we found that treatment of HeLa cells with 2-methyl-5(or -8)-hydroxy-furanonaphthoquinone (FNQ13) induces mitochondrial swelling, followed by apoptosis. This toxic effect of FNQ13 was reduced by the radical scavengers α-tocopherol and trolox. Cytochemical experiments in isolated mitochondria showed that a combination of FNQ13 and NADH induces the production of H2O2 at the exterior mitochondrial membrane surface. This production of H2O2 was reduced by an antibody to the voltage-dependent anion channel (VDAC). Overexpression of the VDAC by transfection with vdac1 cDNA increased the production of H2O2 by HeLa cells, whereas transfection with a small interfering RNA to VDAC reduced FNQ13-induced H2O2 production and cell death due to an almost complete knockdown of VDAC expression. We also found significant correlations between the expression of VDAC and the induction of H2O2 production and cell death by FNQ13 in 11 human cancer cell lines. These results indicate that the anticancer activity of furanonaphthoquinones depends on the production of reactive oxygen species by mitochondrial permeability transition pores (MPTP) including the VDAC.
Authors
Kei-Ichi Hirai
Kanazawa Medical University, Ishikawa, Japan
Hiroki Shimada
Kanazawa Medical University, Ishikawa, Japan
Junko Koyama
Pharmaceutical University, Higashinada, Japan
Yukie Niwa
3Niwa Institute for Immunology, Saiwaicho, Tosashimizu
Shigeomi Shimizu
Osaka University Medical School, Osaka, Japan
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.