Mitotoxin

A mitotoxin is a cytotoxic molecule targeted to specific cells by a mitogen. It is generally found in snake venom. Mitotoxins are responsible for mediating cell death by interfering with protein or DNA synthesis. Some mechanisms by which mitotoxins can interfere with DNA or protein synthesis include the inactivation of ribosomes or the inhibition of complexes in the mitochondrial electron transport chain. 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.

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. Because of the high affinity and specificity of mitotoxin binding, they present the possibility of creating precise therapeutic agents. A major one of these possibilities is the potential usage of growth factor-based mitotoxins as anti-neoplastic agents that can modulate the growth of melanomas.

References

  1. 1 2 3 4 5 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.