Cobra venom cytotoxins; apoptotic or necrotic agents?
- PMID: 26482932
- DOI: 10.1016/j.toxicon.2015.09.017
Cobra venom cytotoxins; apoptotic or necrotic agents?
Abstract
Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent.
Keywords: Apoptosis; Cancer; Cobra venom; Cytotoxin-I; Cytotoxin-II.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Similar articles
-
Current Insights in the Mechanisms of Cobra Venom Cytotoxins and Their Complexes in Inducing Toxicity: Implications in Antivenom Therapy.Toxins (Basel). 2022 Dec 1;14(12):839. doi: 10.3390/toxins14120839. Toxins (Basel). 2022. PMID: 36548736 Free PMC article. Review.
-
The anticancer effect of cytotoxin 1 from Naja atra Cantor venom is mediated by a lysosomal cell death pathway involving lysosomal membrane permeabilization and cathepsin B release.Am J Chin Med. 2013;41(3):643-63. doi: 10.1142/S0192415X13500456. Am J Chin Med. 2013. PMID: 23711147
-
Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis.J Breast Cancer. 2014 Dec;17(4):314-22. doi: 10.4048/jbc.2014.17.4.314. Epub 2014 Dec 26. J Breast Cancer. 2014. PMID: 25548578 Free PMC article.
-
[Purification and anticancer activity of cytotoxin-14 from venom of Naja naja atra].Zhongguo Yao Li Xue Bao. 1993 May;14(3):279-82. Zhongguo Yao Li Xue Bao. 1993. PMID: 8237412 Chinese.
-
Antiproliferative activity of cobra venom cytotoxins.Curr Top Med Chem. 2015;15(7):638-48. doi: 10.2174/1568026615666150217113011. Curr Top Med Chem. 2015. PMID: 25686733 Review.
Cited by
-
Clinical study of anti-snake venom blockade in the treatment of local tissue necrosis caused by Chinese cobra (Naja atra) bites.PLoS Negl Trop Dis. 2022 Dec 16;16(12):e0010997. doi: 10.1371/journal.pntd.0010997. eCollection 2022 Dec. PLoS Negl Trop Dis. 2022. PMID: 36525460 Free PMC article. Clinical Trial.
-
Current Insights in the Mechanisms of Cobra Venom Cytotoxins and Their Complexes in Inducing Toxicity: Implications in Antivenom Therapy.Toxins (Basel). 2022 Dec 1;14(12):839. doi: 10.3390/toxins14120839. Toxins (Basel). 2022. PMID: 36548736 Free PMC article. Review.
-
Development of a Treatment Protocol for Cobra (Naja naja) Bite Envenoming in Dogs.Toxins (Basel). 2020 Nov 2;12(11):694. doi: 10.3390/toxins12110694. Toxins (Basel). 2020. PMID: 33147770 Free PMC article.
-
Phospholipase A2 from krait Bungarus fasciatus venom induces human cancer cell death in vitro.PeerJ. 2019 Dec 3;7:e8055. doi: 10.7717/peerj.8055. eCollection 2019. PeerJ. 2019. PMID: 31824756 Free PMC article.
-
Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models.PLoS Negl Trop Dis. 2020 Feb 7;14(2):e0008054. doi: 10.1371/journal.pntd.0008054. eCollection 2020 Feb. PLoS Negl Trop Dis. 2020. PMID: 32032357 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials