Toxicity of the novel animal-derived anticancer agent, VRCTC-310: acute and subchronic studies in beagle dogs

DeTolla, Louis J.; Stump, Kyle C.; Russell, Robert G.; Viskatis, Luis J.; Vidal, Juan G.; Newman, Robert A.; Etcheverry, Martin A.

doi:10.1016/0300-483x(94)02995-7

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…21) These multiple usages are mainly attributed to its functional heterogeneity, especially the lysis of different cell types. In this study, we have demonstrated that CTX III induces apoptosis in human leukemia K562 cells, consistent with the findings by Yang et al (2005).…”

Section: Discussionmentioning

confidence: 99%

Involvement of p38 and c-Jun N-Terminal Protein Kinase in Cardiotoxin III-Induced Apoptosis of K562 Cells

Chen

Hua-xin

et al. 2009

Biological & Pharmaceutical Bulletin

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Section: Discussionmentioning

confidence: 99%

Involvement of p38 and c-Jun N-Terminal Protein Kinase in Cardiotoxin III-Induced Apoptosis of K562 Cells

Chen

Hua-xin

et al. 2009

Biological & Pharmaceutical Bulletin

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“…10 Cardiotoxins (CTXs), a group of highly basic polypeptides of 60-amino acid residues, present abundantly in the elapid family of snakes, show very diverse pharmacological functions including hemolysis, cytotoxicity and depolarization of muscle. [11][12][13] In our previous studies, CTX III has been shown to induce dose-and time-dependent apoptosis in K562 cells via the intrinsic pathway of apoptosis involving mitochondrial membrane permeability, the release of cytochrome c and subsequent caspase activation. 14,15 Although it appears that CTX III can induce cytotoxicity and apoptotic cell death, the underlying mechanism of this process has not been well elucidated.…”

Section: Introductionmentioning

confidence: 99%

Cardiotoxin III induces c‐jun N‐terminal kinase‐dependent apoptosis in HL‐60 human leukaemia cells

Chien

Yang

et al. 2007

Cell Biochemistry & Function

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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. The molecular effects of CTX III on HL-60 cells were dissected in the present study. We found that the antiproliferative action of CTX III on HL-60 cells was mediated through apoptosis, as characterized by an increase of sub G1 population, DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Upregulation of Bax, downregulation of Bcl-2, the release of mitochondrial cytochrome c to cytosol and the activations of capase-9 and -3 were noted, while CTX III had no appreciable effect on the levels of Bcl-X(L) and Bad proteins. Moreover, c-Jun N-terminal kinase (JNK) was activated shortly after CTX III treatment in HL-60 cells. Consistently, the SP600125 compound, an anthrapyrazolone inhibitor of JNK, suppressed apoptosis induced by CTX III. As expected, this JNK inhibitor also attenuated the modulation of Bax and Bcl-2, as well as the cytosolic appearance of cytochrome c and the activation of caspase-3 and caspase-9 that induced by CTX III. These findings suggest that CTX III can induce apoptosis in HL-60 cells via the mitochondrial caspase cascade and the activation of JNK is critical for the initiation of the apoptotic death of HL-60 cells.

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“…Moreover, the toxins showed preferential cytotoxicity toward cancer cells, probably mediated by inhibiting protein kinase C activity or the membrane fusion effect [7][8][9][10][11]. In our previous studies, Cardiotoxin III (CTX III) had been demonstrated to induce dose-and time-dependent apoptosis in K562 cells via the intrinsic pathway of apoptosis involving mitochondrial membrane permeability, the release of cytochrome c, and resulting caspase activation [12,13].…”

Section: Introductionmentioning

confidence: 99%

Cardiotoxin III‐induced apoptosis is mediated by Ca²⁺‐dependent caspase‐12 activation in K562 cells

Yang

Chien

Chang

et al. 2008

J Biochem & Molecular Tox

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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. When K562 cells were treated with CTX III, cytosolic calcium concentration was rapidly and persistently increased. This CTX III-induced cell death was partially reversed by pretreatment with BAPTA/AM (20 microM), a chelator of intracellular Ca2+. Moreover, CTX III-induced apoptotic signals, such as caspase-12 and c-Jun N-terminal kinase (JNK) activation, were induced in a time-dependent manner and inhibited by BAPTA/AM. In contrast, the neutral protease micro-calpain, a key enzyme in endoplasmic reticulum (ER) stress-related apoptosis via caspase-12 activation, was unchanged during apoptosis. Taken together, our findings suggest CTX III-induced apoptosis is triggered by Ca2+ influx, then activated caspase-12 and JNK through micro-calpain-independent cascade, and consequently caused apoptosis.

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Toxicity of the novel animal-derived anticancer agent, VRCTC-310: acute and subchronic studies in beagle dogs

Cited by 12 publications

References 30 publications

Involvement of p38 and c-Jun N-Terminal Protein Kinase in Cardiotoxin III-Induced Apoptosis of K562 Cells

Involvement of p38 and c-Jun N-Terminal Protein Kinase in Cardiotoxin III-Induced Apoptosis of K562 Cells

Cardiotoxin III induces c‐jun N‐terminal kinase‐dependent apoptosis in HL‐60 human leukaemia cells

Cardiotoxin III‐induced apoptosis is mediated by Ca²⁺‐dependent caspase‐12 activation in K562 cells

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Toxicity of the novel animal-derived anticancer agent, VRCTC-310: acute and subchronic studies in beagle dogs

Cited by 12 publications

References 30 publications

Involvement of p38 and c-Jun N-Terminal Protein Kinase in Cardiotoxin III-Induced Apoptosis of K562 Cells

Involvement of p38 and c-Jun N-Terminal Protein Kinase in Cardiotoxin III-Induced Apoptosis of K562 Cells

Cardiotoxin III induces c‐jun N‐terminal kinase‐dependent apoptosis in HL‐60 human leukaemia cells

Cardiotoxin III‐induced apoptosis is mediated by Ca2+‐dependent caspase‐12 activation in K562 cells

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Cardiotoxin III‐induced apoptosis is mediated by Ca²⁺‐dependent caspase‐12 activation in K562 cells