Cryptophycin

Cryptophycin is a potent cytotoxin produced by cyanobacteria of the genus Nostoc. It is also a promising drug in many cancer therapies.

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Mode of Operation

Cryptophycin works by attacking the tubulin microfilaments found in eukaryotic cells and thereby preventing cell division and reproduction. The main hypothesis as to why the blue-green algae produce this energetically expensive compound is that it is used as a strong anti-fungal agent in order to prevent fungus or other types of algae from competing with the blue-green algae for nutrients and sunlight. This is necessary because the algae have no means of physically evading organisms that would settle on them or above them and block the sunlight that they need in order to photosynthesize. It has been found that the amount of cryptophycin being produced by any one alga at any given time depends on the current environmental conditions. The compound must be able to distinguish between destroying those microtubules that are foreign and its own cells so it has evolved to recognize cells which are proliferating too quickly to be its own cells by an as yet unknown mechanism. This property of cryptophycin allows it to recognize cancerous tumor cells, even those of “solid tumors” such as those in brain, colon, ovarian, prostate, pancreas, lung and breast cancers and it can destroy the cells of multi-drug resistant (MDR) tumors. These are the cancers that chemotherapy has the least ability to treat and account for eighty-five percent of all cancer deaths in the United States (Back, 2005).

Cryptophycin and the Preservation of Biodiversity

Botanical sources have historically been the origin of the majority of drugs and precursors to pharmaceutical agents. Seventy-four percent of current anticancer drugs are either natural products or have been derived directly from natural products (Tan, 2006). Thus the importance of the maintenance of biodiversity as it applies to crytophycin are twofold; first, it was originally discovered from an extant population in the wild, and secondly, because it is so difficult and expensive to produce synthetically, due to the compound’s complex molecular structure it is important to maintain wild populations. Cryptophycin’s synthesis in a lab is the product of thirty-five steps with a yield of only 3.5% (Moore et al., 1996). Currently, the only source from which it can be harvested in any viable amount is from the Nostoc cyanobacteria themselves. Some other secondary metabolites that are currently being tested as potential cures for other diseases such as Curacin A, which is FDA approved to treat gout, are produced by organisms that are endemic to only one specific locale, in this case, the cyanobacteria species Lyngbya majuscule, which is found only off the coast of Curacao. These findings help emphasize the large amount of chemical diversity present in the cyanobacteria and the need to preserve this biodiversity not only for its own sake, but for the continued discovery of valuable medicinal agents. This also indicates that on some level, the preservation of biological resources should focus on chemotypes and biodiversity in phyla rather than solely on individual species counts.

Current Progress

Cryptophycin is now being tested in Phase 1 Human Clinical Trials and in January of this year a study was published by University of Michigan Life Sciences Institute Research Professor David H. Sherman and researcher Zachary Q. Beck which indicated that they are still attempting to create synthetic cryptophycin analogs in their lab to be used for further human clinical trials.[1]

References

1. Charles D. Smith et al., “Cryptophycin: A New Antimicrotubule Agent Active against Drug-resistant Cells,” Cancer Research 54, 3779-3784 (1994).

2. NR Watts et al., “The cryptophycin-tubulin ring structure indicates two points of curvature in the tubulin dimer,” Biochemistry 42, 12662-12669 (2002).

3. G. Tan, C. Gyllenhaal, D.D. Soejarto, “Biodiversity as a Source of Anticancer Drugs,” Current Drug Targets 7, 265-277 (2006).

4. Moore RE, et al., “The search for new anti-tumor drugs from blue-green algae,” Current Pharmaceutical Design, 2, 317-330 (1996).

5. Stephen Back, Jian Liang, “Production of cryptophycin from blue-green algae,” The Journal of Young Investigators, 12, (2005).

See also: [http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2000/39/i46/abs/bi0010827.html Interaction of the Antitumor Compound Cryptophycin-52 with Tubulin

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