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University of Florida researchers have modified a toxic chemicalproduced by tiny marine microbes and successfully deployed itagainst laboratory models of colon cancer . Writing in ACS Medicinal Chemistry Letters, UF medicinal chemistsdescribe how they took a generally lethal byproduct of marinecyanobacteria and made it more specifically toxic - to cancer cells. When the scientists gave low doses of the compound to mice with aform of colon cancer, they found that it inhibited tumor growthwithout the overall poisonous effect of the natural product. Evenat relatively high doses, the agent was effective and safe. "Sometimes nature needs a helping human hand to further optimizethese products of evolution to treat human diseases," said HendrikLuesch, Ph.D., an associate professor of medicinal chemistry atUF's College of Pharmacy. "Based on what we learned aboutapratoxins' mechanism of action, we knew this compound class hadgreat potential for use in anticancer therapies; however, thenatural product itself is too toxic to become a therapeutic." The researchers synthesized several apratoxin compounds that weresimilar to the original except for slight differences incomposition, designing one that proved to be extremely potentagainst the cancer cells in cultures and in mice, but without theoverwhelming toxicity. The compound acts as a single agent to reduce levels of two typesof proteins that are targeted by cancer research labs around theworld - growth factors, and enzymes called tyrosine kinases, whichact as receptors for the growth factors. Known as apratoxin S4, the compound strips colon cancer cells oftheir ability to both secrete and use naturally occurring factorsthat fuel growth - something that Luesch, postdoctoral chemistOi-Yen Chen, Ph.D., and assistant scientist Yanxia Liu, Ph.D., sayis a powerful "one-two punch" against mushrooming populations ofcancer cells. The trio describes apratoxin's dual action for the first time intoday's online publication, although Luesch presented earlyfindings in May at the New York Academy of Sciences. "This is an extremely interesting discovery that may have thepotential to lead to a novel drug, but an extraordinary amount ofadditional research is needed before we will know. We can hope,"said David J. Newman, D.Phil., chief of the National CancerInstitute's Natural Products Branch, who was not involved in theresearch. "Luesch has found a novel compound and a novel mechanismof action that stops the secretion of the receptor and the growthfactor - as far as I am aware, this mechanism has only been shownin apratoxin at this time. If nothing else, he has shown us a newway to kill tumor cells and has revealed a new chemistry, and thoseare important steps." Apratoxin is produced by cyanobacteria, microbes that have evolvedtoxins to fend off predators and cope with harsh conditions in amarine environment. Collectively known as blue-green algae - amisnomer because the single-celled organisms are not algae ormembers of the plant kingdom - a wide variety of cyanobacteriaspecies exists in both sea and freshwater environments. Like plants, cyanobacteria convert sunlight into energy through aprocess known as photosynthesis. But where plants exclusively use agreen pigment called chlorophyll to capture light to make food,cyanobacteria also use a bluish pigment called phycocyanin. In addition, cyanobacteria have the unique ability to userespiration as well as photosynthesis to acquire energy, makingthese organisms tiny chemical factories capable of producing manyas-yet unidentified molecules that may be useful for healthapplications. "Marine cyanobacteria produce a huge diversity of compounds," saidLuesch, who is also a member of the UF Shands Cancer Center. "Abouthalf of anticancer drugs are based on natural products. All but acouple of them are derived from terrestrial organisms, yet morethan 70 percent of the Earth is covered by oceans, which presumablycontain a number of therapeutic molecules with potentially novelbiological activities. When we studied the biological effects ofapratoxin, we predicted it would be particularly useful againstcolon cancer if we could engineer it to be more selective." Chen synthesized the apratoxins, while Liu carried out the biologyand pharmacology experiments. More lab work is required before adrug based on apratoxin can be tested in patients with coloncancer, but Luesch believes apratoxin S4 is the first candidate toshow the needed tumor selectivity, antitumor effects and potency tobe effective. The UF Research Opportunity Fund and theBankhead-Coley Cancer Research Program supported the study. Additional References Citations. The e-commerce company in China offers quality products such as Alu Zinc Steel Manufacturer , Laminated Steel, and more. For more , please visit Printed Tinplate today!
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