RRC ID 42772
Author Simamura E, Hirai K, Shimada H, Koyama J, Niwa Y, Shimizu S.
Title Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production of reactive oxygen species by the mitochondrial voltage-dependent anion channel.
Journal Cancer Biol. Ther.
Abstract The mitochondrial production of reactive oxygen species 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 alpha-tocopherol and trolox. Cytochemical experiments in isolated mitochondria showed that a combination of FNQ13 and NADH induces the production of H(2)O(2) at the exterior mitochondrial membrane surface. This production of H(2)O(2) 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 H(2)O(2) by HeLa cells, whereas transfection with a small interfering RNA to VDAC reduced FNQ13-induced H(2)O(2) 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 H(2)O(2) 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 including the VDAC.
Volume 5(11)
Pages 1523-9
Published 2006-11
DOI 10.4161/cbt.5.11.3302
PII 3302
PMID 17012850
MeSH Antineoplastic Agents / pharmacology Apoptosis / drug effects* HeLa Cells / drug effects HeLa Cells / ultrastructure Humans Ion Channels / drug effects Ion Channels / physiology* Mitochondria / drug effects Mitochondria / physiology* Naphthoquinones / pharmacology* Reactive Oxygen Species / metabolism*
IF 3.373
Times Cited 41
Human and Animal Cells