Drug Combination Targets Cancer Cell Cytoskeleton

Cancer researchers have found that combining the chemotherapeutic drug etoposide with ML-7, a protein that inhibits myosin light chain kinase and disrupts cellular cytoskeleton structure, creates a potent treatment agent for mammary and prostate cancers.

Investigators at the University of Illinois (Chicago, IL, USA) worked with isolated tumor cells in culture as well as with mice with mammary tumors and rats with prostate tumors. They mixed ML-7, which inhibits myosin light chain kinase (MLCK) and induces apoptosis in transformed and non-transformed cells, with etoposide, an approved chemotherapeutic agent of the topoisomerase II inhibitor family.

Results published in the May 3, 2006, issue of the European Journal of Cancer showed that the ML-7 in the mixture stimulated the ability of etoposide to induce apoptosis in cultures of Mm5MT mouse mammary adenocarcinoma cells and Mat-Ly-Lu rat prostate cancer cells. In animal studies, ML-7 significantly stimulated the ability of etoposide to prevent the growth of established mammary tumors in mice and prostate tumors in rats.

These results suggest that the addition of ML-7, which is well tolerated with no apparent side affects, could allow reduction in the dosage of etoposide, which has several adverse side effects. "Reducing the dose of the drug without losing effectiveness would have important clinical benefits,” said senior author Dr. Primal de Lanerolle, professor of physiology and biophysics at the University of Illinois. "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.”



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