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Cardiotoxin III induces apoptosis in T24 cells via reactive oxygen species‐independent mitochondrial death pathway
Author(s) -
Chien ChingMing,
Yang ShengHuei,
Lu MeiChin,
Chang LongSen,
Lin ShinneRen
Publication year - 2004
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10415
Subject(s) - apoptosis , reactive oxygen species , cytochrome c , cardiolipin , mitochondrion , dna fragmentation , poly adp ribose polymerase , biology , cytosol , population , mitochondrial apoptosis induced channel , microbiology and biotechnology , cardiotoxin , biochemistry , chemistry , programmed cell death , polymerase , dna , membrane , enzyme , venom , medicine , phospholipid , environmental health
Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. CTX III inhibited the growth of T24 cells in a time‐ and dose‐dependent manner with an IC 50 value of 1.7 µg/mL and displayed several features of apoptosis including apoptotic body formation, increase of sub G 1 population, DNA fragmentation, and poly (ADP‐ribose) polymerase (PARP) cleavage. Using apoptosis analysis, measurement of reactive oxygen species (ROS) and assessment of mitochondrial membrane potentials (ΔΨm), CTX III was found to be a potent inducer of apoptosis, transducing apoptotic signals via a decrease in mitochondrial membrane potential (ΔΨm) and release of cytochrome c from mitochondria into cytosol. However, CTX III did not generate reactive oxygen species (ROS). Taken together, the present data indicate that CTX III induces apoptosis in T24 cells through an ROS‐independent mitochondrial dysfunction pathway and resultant cytochrome c release. This is the first report on the mechanism of the anticancer effect of CTX III on T24 cells. Drug Dev. Res. 63:219–224, 2004. © 2004 Wiley‐Liss, Inc.