Anti-cancer agent stops metastasis in its tracks....

Like microscopic inchworms, cancer cells slink away from tumors to travel and settle elsewhere in the body. Now, researchers at Weill Cornell Medical College, have found  that new anti-cancer agent, i.e., macroketone (see structure) break down the loping gait these cells use to migrate, stopping them in their tracks.

As per the claim by the lead researcher, Dr. Xin-Yun Huang, a professor in the Department of Physiology and Biophysics at Weill Cornell Medical College, mice implanted with cancer cells and treated with the small molecule macroketone lived a full life without any cancer spread, compared with control animals, which all died of metastasis. When macroketone was given a week after cancer cells were introduced, it still blocked greater than 80 percent of cancer metastasis in mice. He further adds that, these findings provide a very encouraging direction for development of a new class of anti-cancer agents, the first to specifically stop cancer metastasis. 

Dr. Huang and his research team have been working on macroketone since 2003. Their work started after researchers in Japan isolated a natural substance, dubbed migrastatin, secreted by Streptomyces bacteria, that is the basis of many antibiotic drugs. The Japanese researchers noted that migrastatin had a weak inhibitory effect on tumor cell migration. After a lot of modifications, researchers made several versions that were a thousand-fold more potent than the original. In 2005, they published a study showing that several of the new versions, including macroketone, stopped cancer cell metastasis in laboratory animals, but they didn't know how the agent worked. 

Interestingly, in the current study, the researchers revealed the mechanism. As per the claim  macroketone targets an actin cytoskeletal protein known as fascin that is critical to cell movement. In order for a cancer cell to leave a primary tumor, fascin bundles actin filaments together like a thick finger. The front edge of this finger creeps forward and pulls along the rear of the cell. Cells crawl away in the same way that an inchworm moves. Macroketone latches on to individual fascin, preventing the actin fibers from adhering to each other and forming the pushing leading edge Because individual actin fibers are too soft when they are not bundled together, the cell cannot move.

Researchers conclude that, the new animal experiments detailed in the study confirmed the power of macroketone. The agent did not stop the cancer cells implanted into the animals from forming tumors or from growing.

"This suggests to us that an agent like macroketone could be used to both prevent cancer spread and to treat it as well," Dr. Huang says. "Of course, because it has no effect on the growth of a primary tumor, such a drug would have to be combined with other anti-cancer therapies acting on tumor cell growth."

 Ref : http://weill.cornell.edu/news/releases/wcmc/wcmc_2010/04_14_10.shtml