Although tumor growth depends on the rapid cell division and mobility of cancer cells -- processes highly dependent on the cytoskeleton -- the cytoskeleton has not been a target in treating cancer, said Primal de Lanerolle, professor of physiology and biophysics at the University of Illinois at Chicago and principal author of the study.
The researchers found that ML-7, which inhibits an enzyme called myosin light chain kinase, which is important to the structure and dynamics of the cytoskeleton, induces cell suicide, or apoptosis, in cultured breast and prostate cancer cell lines. In addition, treatment with ML-7 in combination with etoposide, a chemotherapy drug used to treat solid tumors, enhanced the ability of etoposide to kill cancer cells.
In animal models, ML-7 retarded growth of breast cancer and prostate cancer tumors. The combination of ML-7 and etoposide reduced tumor growth by 88.5 percent for the breast cancer tumors and by 79.1 percent in the prostate cancer tumors compared to controls.
Like many chemotherapy drugs, etoposide can have adverse side effects.
"Reducing the dose of the drug without losing effectiveness would have important clinical benefits," said de Lanerolle. "ML-7 seemed to be tolerated very well, without any overt toxic side effects of its own."
The study suggests an entirely new target for cancer therapies, de Lanerolle said. "Our study supports the idea that the cytoskeleton is important in determining whether cells live or die, and that destabilizing the cytoskeleton may be a good way to induce apoptosis in cancer cells."
Researchers now must test ML-7 for toxicity and perform further preliminary animal experiments before human trials could be planned. Only a tiny fraction of promising candidate drugs enter clinical trials, and few of those are approved.
Lian-Zhi Gu, We-Yang Hu and Nenad Antic of UIC, Rajendra Mehta of the Illinois Institute of Technology Research Institute, and Jerrold Turner of the University of Chicago collaborated in the study. The study was supported in part by grants from the National Institutes of Health. Wen-Yang Hu is supported by the American Heart Association.
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Journal
European Journal of Cancer