Newswise — A molecule that interferes with the internal scaffolding that shapes the cell may kill cancer cells, retard the growth of tumors and give a boost toa common chemotherapy drug, according to findings appearing in the May 3issue of the European Journal of Cancer.
Although tumor growth depends on the rapid cell division and mobility ofcancer cells -- processes highly dependent on the cytoskeleton -- thecytoskeleton has not been a target in treating cancer, said Primal deLanerolle, professor of physiology and biophysics at the University ofIllinois at Chicago and principal author of the study.
The researchers found that ML-7, which inhibits an enzyme called myosinlight chain kinase, which is important to the structure and dynamics of thecytoskeleton, induces cell suicide, or apoptosis, in cultured breast andprostate cancer cell lines. In addition, treatment with ML-7 in combinationwith etoposide, a chemotherapy drug used to treat solid tumors, enhancedthe ability of etoposide to kill cancer cells.
In animal models, ML-7 retarded growth of breast cancer and prostate cancertumors. The combination of ML-7 and etoposide reduced tumor growth by 88.5percent for the breast cancer tumors and by 79.1 percent in the prostatecancer tumors compared to controls.
Like many chemotherapy drugs, etoposide can have adverse side effects.
"Reducing the dose of the drug without losing effectiveness would haveimportant clinical benefits," said de Lanerolle. "ML-7 seemed to betolerated very well, without any overt toxic side effects of its own."
The study suggests an entirely new target for cancer therapies, deLanerolle said. "Our study supports the idea that the cytoskeleton isimportant in determining whether cells live or die, and that destabilizingthe cytoskeleton may be a good way to induce apoptosis in cancer cells."
Researchers now must test ML-7 for toxicity and perform further preliminaryanimal experiments before human trials could be planned. Only a tinyfraction of promising candidate drugs enter clinical trials, and few ofthose are approved.
Lian-Zhi Gu, We-Yang Hu and Nenad Antic of UIC, Rajendra Mehta of theIllinois Institute of Technology Research Institute, and Jerrold Turner ofthe University of Chicago collaborated in the study. The study wassupported in part by grants from the National Institutes of Health.Wen-Yang Hu is supported by the American Heart Association.
UIC ranks among the nation's top 50 universities in federal researchfunding and is Chicago's largest university with 25,000 students, 12,000faculty and staff, 15 colleges and the state's major public medical center.A hallmark of the campus is the Great Cities Commitment, through which UICfaculty, students and staff engage with community, corporate, foundationand government partners in hundreds of programs to improve the quality oflife in metropolitan areas around the world.
For more information about UIC, visit http://www.uic.edu
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