In vitro comparison of cytotoxic effects of crotoxin against three human tumors and a normal human epidermal keratinocyte cell line

Rudd, Colette J.; Viskatis, Luis J.; Vidal, Juan C.; Etcheverry, Martin A.

doi:10.1007/bf00873958

Cited by 39 publications

(33 citation statements)

References 5 publications

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“…CrTX is a potent antitumor agent and displays cytotoxic activity against a variety of murine and human tumor cell lines in vitro [15,16] . It requires both the PLA 2 activity of subunit B [15] and the ability of the complex to dissociate into their subunits [15,29] .…”

Section: Discussionmentioning

confidence: 99%

“…Its cytotoxicity was independent of cell growth since both quiescent and proliferating cells had similar sensitivities. CrTX displays cytotoxic activity against a variety of murine [15] and human tumor cell lines in vitro [16] and appears to be highly active toward cell lines expressing a high density of epidermal growth factor receptors (EGFR) [17] ; however, the precise mechanism of the cytotoxicity remains to be determined. It had previously been assumed that the toxin simply induces lysis through the disruption of the cell membrane.…”

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confidence: 99%

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Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Yan

Yang

Qin

et al. 2007

Acta Pharmacologica Sinica

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Aim: To investigate the role of crotoxin (CrTX)‐induced autophagy in the death of MCF‐7 cells, a caspase‐3‐deficient, human breast cancer cell line. Methods: Cultured MCF‐7 cells were treated with various doses of CrTX, a phospholipase A2 (PLA2) isolated from the venom of the South American rattlesnake, Crotalus durissus terrificus. The cytotoxicity of CrTX in the presence and absence of caspase inhibitors was measured with methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) leakage assays. The activation of autophagy was determined with transmission electron microscope and monodansylcadaverin (MDC) labeling. The upregulation of lysosomal enzymes, the release of cyto‐chrome c (cyto‐c), and the nuclear translocation of the apoptosis inducing factor (AIF) were examined by immunoblotting and immunofluorescence. Results: CrTX inhibited the viability of MCF‐7 cells in a dose‐ and time‐dependent manner. CrTX‐activated autophagy was revealed by punctuate MDC labeling, and an increase in the formation of autophagosomes as well as apoptosis, as evidenced by nuclear condensation and fragmentation. The activation of cathepsin B, D, and L, in addition to the release of cytochrome c and the relocation of AIF into nuclei, were observed after CrTX treatment. Autophagy inhibitors 3‐methyladenine (3‐MA), NH4Cl, and the pan‐caspase inhibitor, Z‐Val‐Ala‐Asp‐fluoromethylketone (Z‐Vad‐fmk), attenuated CrTX‐induced cell death. Conclusion: An autophagic mechanism contributes to the apoptosis of MCF‐7 cells induced by CrTX.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Yan

Yang

Qin

et al. 2007

Acta Pharmacologica Sinica

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“…CrTX is a potent antitumor agent, which has cytotoxic activity against a variety of human tumor cell lines in vitro (6,7,15). CrTX also exerts an anti-inflammatory/analgesic activity seemingly through the lipoxygenase pathway without negatively impacting its anticancer activity.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies recently have shown that CrTX also has immunomodulatory, anti-inflammatory, antimicrobial and analgesic actions. Studies have also reported that CrTX has antitumor effects (6). However, the pathway to programmed cell death remains to be clearly determined and may be tumor-dependent (7,8).…”

Section: Introductionmentioning

confidence: 99%

Crotoxin enhances the antitumor activity of gefinitib (Iressa) in SK-MES-1 human lung squamous carcinoma cells

Wang

Xie

et al. 2012

Oncol Rep

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Abstract. Crotoxin (CrTX), a neurotoxin, is isolated from the venom of South American rattlesnakes and has potent antitumor activity. Here, we investigated the antitumor effect of CrTX on the SK-MES-1 human lung squamous cell carcinoma cell line that has acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. CrTX caused G1 arrest and p-JNK protein upregulation that resulted in apoptosis of SK-MES-1 cells. SP600125, a specific inhibitor of p-JNK, could rescue SK-MES-1 cells from CrTX-induced apoptosis. CrTX and gefinitib (Iressa) both inhibited the viability and proliferation of SK-MES-1 cells in a dose-and time-dependent manner. The combination of CrTX and Iressa significantly enhanced the antitumor activity of Iressa. In vivo studies revealed that CrTX caused increased damage to blood vessels and reduced tumor size when combined with Iressa. The present study showed that the JNK signal transduction pathway mediated the anti-apoptotic effect of CrTX, and furthermore, CrTX could enhance the antitumor effect of tyrosine kinase inhibitors in cells with acquired resistance.

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“…Crotoxin displays cytotoxic activity against a variety of murine and human tumor cell line in vitro (Rudd et al, 1994). Crotoxin induced cytotoxic effects appear to be highly selective towards cell line expressing high density of epithelial growth factor receptor.…”

Section: Anticancer Activity Of Snake Venommentioning

confidence: 99%

Snake Venom: A Potent Anticancer Agent

Jain

Kumar²

2012

Asian Pacific Journal of Cancer Prevention

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Since cancer is one of the leading causes of death worldwide, and there is an urgent need to find better treatment. In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. Treatment modalities comprise radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Currently, the use of chemotherapeutics remains the predominant option for clinical control. However, one of the major problems with successful cancer therapy using chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. This has led to the increased use of anticancer drugs developed from natural resources. The biodiversity of venoms and toxins makes them a unique source from which novel therapeutics may be developed. In this review, the anticancer potential of snake venom is discussed. Some of the included molecules are under clinical trial and may find application for anticancer drug development in the near future.

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In vitro comparison of cytotoxic effects of crotoxin against three human tumors and a normal human epidermal keratinocyte cell line

Cited by 39 publications

References 5 publications

Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Crotoxin enhances the antitumor activity of gefinitib (Iressa) in SK-MES-1 human lung squamous carcinoma cells

Snake Venom: A Potent Anticancer Agent

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