A mitotoxin is a cytotoxic molecule targeted to specific cells by a mitogen. Generally found in snake venom. Mitotoxins are responsible for mediating cell death [1] by interfering with protein or DNA synthesis.[2] Some mechanisms by which mitotoxins can interfere with DNA or protein synthesis include the inactivation of ribosomes [1] or the inhibition of complexes in the mitochondrial electron transport chain.[3] These toxins have a very high affinity and level of specificity for the receptors that they bind to. Mitotoxins bind to receptors on cell surfaces and are then internalized into cells via receptor-mediated endocytosis. Once in the endosome, the receptor releases its ligand and a mitotoxin can mediate cell death.[1]
There are different classes of mitotoxins, each acting on a different type of cell or system. The mitotoxin classes that have been identified thus far include: interleukin-based, transferrin based, epidermal growth factor-based, nerve growth factor-based, insulin-like growth factor-I-based, and fibroblast growth factor-based mitotoxins.[1] Because of the high affinity and specificity of mitotoxin binding, they present the possibility of creating precise therapeutic agents.[1] A major one of these possibilities is the potential usage of growth factor-based mitotoxins as anti-neoplastic[4] agents that can modulate the growth of melanomas.[5]
References
edit- ^ a b c d e Lappi, Douglas A.; Baird, Andrew (January 1990). "Mitotoxins: Growth factor-targeted cytotoxic molecules". Progress in Growth Factor Research. 2 (4): 223–236. doi:10.1016/0955-2235(90)90020-k. ISSN 0955-2235. PMID 2133290.
- ^ Lappi, Douglas A.; Maher, Pamela A.; Martineau, Darlene; Baird, Andrew (April 1991). "The basic fibroblast growth factor-saporin mitotoxin acts through the basic fibroblast growth factor receptor". Journal of Cellular Physiology. 147 (1): 17–26. doi:10.1002/jcp.1041470104. ISSN 0021-9541. PMID 1645359. S2CID 30877555.
- ^ Souders, Christopher L.; Wei, Chi; Schmidt, Jordan T.; Da Fonte, Dillon F.; Xing, Lei; Trudeau, Vance L.; Martyniuk, Christopher J. (May 2021). "Mitochondria of teleost radial glia: A novel target of neuroendocrine disruption by environmental chemicals?". Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 243: 108995. doi:10.1016/j.cbpc.2021.108995. ISSN 1532-0456. PMID 33545344. S2CID 231918972.
- ^ Kreitman, Robert J (February 2000). "Chimeric toxins in cancer treatment". Emerging Drugs. 5 (1): 61–71. doi:10.1517/14728214.5.1.61. ISSN 1361-9195. S2CID 85995595.
- ^ Ying, Martineau (1 August 1994). "Anti-B16-F10 melanoma activity of a basic fibroblast growth factor-saporin mitotoxin". Cancer. 74 (3): 848–853. doi:10.1002/1097-0142(19940801)74:3<848::AID-CNCR2820740310>3.0.CO;2-J. PMID 8039113. S2CID 25353960.
- "(WO/1995/003831) Monogenous preparations of cytotoxic conjugates field of the invention". World Intellectual Property Organization. 1995. pp. para. 28. Archived from the original on 2011-06-05. Retrieved 2008-05-03.
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