The mechanism of cytotoxicity by Naja naja atra cardiotoxin 3 is physically distant from its membrane-damaging effect.
In order to dissect out whether multiple activities of cardiotoxins (CTXs) are connected, to some extent, with each other, studies on reduced and S-carboxyamidomethylated (Rcam) Naja naja atra CTX3 were carried out in the present study. Although both CTX3 and Rcam-CTX3 induced apoptotic death of PC-3 cells as evidenced by propodium iodide/annexin V double staining, degradation of procaspases and DNA fragmentation, the cytotoxicity of Rcam-CTX3 was mostly 100-fold lower than that noted with native toxin. However, Rcam-CTX3 retained approximately 38% of the membrane-damaging activity of native toxin as revealed by the decrease in calcein self-quenching from phospholipid vesicles. These results are likely to reflect that the mechanism of cytotoxicity by CTX3 is not heavily dependent on its membrane-perturbing effect, and suggest that the structural elements within CTX3 responsible for the two activities are probably separated.
Chen
Ku-Chung
KC
Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
Kao
Pei-Hsiu
PH
Lin
Shinne-Ren
SR
Chang
Long-Sen
LS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D017815:Elapidae / Q000502:physiology*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000187:drug effects*; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology
D003603:Cytotoxins; D004546:Elapid Venoms; D008051:Lipid Bilayers; D008081:Liposomes; D008565:Membrane Proteins; C055953:cobra cytotoxin III; D020169:Caspases