Cardiotoxin III induces apoptosis in T24 cells via reactive oxygen species‐independent mitochondrial death pathway

Abstract

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 mg/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 (DCm), CTX III was found to be a potent inducer of apoptosis, transducing apoptotic signals via a decrease in mitochondrial membrane potential (DCm) 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.

Concomitant inactivation of the epidermal growth factor receptor, phosphatidylinositol 3‐kinase/Akt and Janus tyrosine kinase 2/signal transducer and activator of transcription 3 signalling pathways in cardiotoxin III‐treated A549 cells

“…These toxins show preferential cytotoxicity towards cancer cells, probably mediated by inhibition of protein kinase C activity or through a membrane fusion effect 18–20 . Previous studies have shown that CTX III exhibits cytotoxic activity against T24 (human bladder cancer), K562 and HL‐60 (human leukaemia), Colo205 (human colorectal cancer), MCF‐7 (human breast adenocarcinoma) and Ca9‐22 (oral squamous cell carcinoma) cells 21–27 . Nevertheless, the cellular signalling pathways involved in these effects of CTX III remain unknown.…”

“…[18][19][20] Previous studies have shown that CTX III exhibits cytotoxic activity against T24 (human bladder cancer), K562 and HL-60 (human leukaemia), Colo205 (human colorectal cancer), MCF-7 (human breast adenocarcinoma) and Ca9-22 (oral squamous cell carcinoma) cells. [21][22][23][24][25][26][27] Nevertheless, the cellular signalling pathways involved in these effects of CTX III remain unknown. In the present study, the apoptotic effects of CTX III on A549 cells were investigated, with particular emphasis on the signalling pathways involved.…”