Natural products for cancer chemotherapy.
Bottom Line: A vast array of biological metabolites can be obtained from the marine world, which can be used for effective cancer treatment.In addition, the high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side-effects increase the demand for novel anti-tumour drugs active against untreatable tumours, with fewer side-effects and/or with greater therapeutic efficiency.This review points out those technologies needed to produce the anti-tumour compounds of the future.
Affiliation: Charles A Dana Research Institute for Scientists Emeriti, Drew University, Madison, NJ 07940, USA. email@example.comShow MeSH
Related in: MedlinePlus
Mentions: An unusual source of secondary metabolites are the myxobacteria, relatively large Gram‐negative rods which move by gliding or creeping. They form fruiting bodies and have a very diverse morphology. Over 400 compounds had been isolated from these organisms by 2005, but the first in clinical trials were the epothilones, potential anti‐tumour agents, which act like taxol (see Plant anti‐tumour agents below) but are active versus taxol‐resistant tumours (Kowalski et al., 1997). Epothilones are 16‐member ring polyketide macrolide lactones produced by the myxobacterium Sorangium cellulosum, which were originally developed as antifungal agents against rust fungi (Gerth et al., 1996; 2000), but have found their use as anti‐tumour compounds. Their structures are shown in Fig. 3 (Goodin et al., 2004). They contain a methylthiazole group attached by an olefinic bond. They are active against breast cancer and other forms of cancer (Chou et al., 1998). They bind to and stabilize microtubules essential for DNA replication and cell division, even more so than taxol. One epothilone, ixebepilone (Ixempra), produced chemically from epothilone B and which targets microtubules, has been recently approved by FDA. By preventing the disassembly of microtubules, epothilones cause arrest of the tumour cell cycle at the GM2/M phase and induce apoptosis. The mechanism is similar to that of taxol but epothilones bind to tubulin at different binding sites and induce microtubule polymerization. Production of epothilone B by S. cellulosum is accompanied by the undesirable epothilone A. Production of epothilone B over A is favoured by adding sodium propionate to the medium. Epothilone polyketides are more water‐soluble than taxol. The epothilone gene cluster has been cloned, sequenced, characterized and expressed in the faster growing S. coelicolor, resulting in the production of epothilones A and B (Julien et al., 2000; Tang et al., 2000).
Affiliation: Charles A Dana Research Institute for Scientists Emeriti, Drew University, Madison, NJ 07940, USA. firstname.lastname@example.org