A new study funded by a grant from the Department of Defense Breast Cancer Program and the National Institutes of Health and conducted by Researchers at the University of Missouri, shows that the oxidosqualene cyclase inhibitor RO 48-8071, a compound initially developed by Roche Pharmaceuticals as a cholesterol-fighting molecule, not only halts the progression of breast cancer, but also can kill the cancerous cells. The findings were published in the May 31, 2014 issues ofBreast Cancer Research and Treatment.
Previous studies have shown that in nearly 70% of breast cancers found in women, tumor progression depends on estrogen, a group of compounds named for their importance in both menstrual and estrous reproductive cycles. This means that these tumors can be treated with anti-hormone medicines such as tamoxifen (Nolvadex?;AstraZeneca/Soltamox?/DARA BioSciences). Although most hormone-responsive tumors respond to anti-estrogen therapies, they eventually develop resistance. The researchers wanted to find and identify an alternative target involved in the regulation of breast cancer progression.
…further clinical testing can lead to a drug that has the dual purpose of fighting high cholesterol and cancer…
“Cholesterol is a molecule found in all animal cells and serves as a structural component of cell membranes,” explained Salman M. Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Centerat the University of Missouri,Columbia, MO. “Because tumor cells grow rapidly they need to synthesize more cholesterol. Scientists working to cure breast cancer often seek out alternative targets that might slow or stop the progression of the disease, including the elimination of the cancerous cells. In our study, we targeted the production of cholesterol in cancer cen. Although tumor cells may initially respond to therapies, most eventually develop resistance which causes breast cancer cells to grow and spread.”
Attractive therapeutic pathways
Cholesterol also can contribute to the development of anti-hormone resistance because cholesterol is converted into hormones in tumor cells. Therefore, these cholesterol-forming pathways are attractive therapeutic targets for the treatment of breast cancer.
Using compounds initially developed by Roche Pharmaceuticals for the treatment of high cholesterol, which reduces cholesterol in a different manner than the widely used statins, Hyder and his team administered the molecule to human breast cancer cells. They found that the compound was effective in reducing human breast cancer cell growth and often caused cancer cell death. Most interestingly they found that the cholesterol lowering drug they tested destroyed an estrogen receptor, a protein which encourages the tumor cells to grow.
Effective in killing cancer cells
Equipped with this information, Hyder and the team tested the results in mice with breast cancer. Following injection of the compound, Hyder found that the molecule was effective at killing breast cancer cells by reducing the presence of estrogen receptors in tumor cells, Hyder said.
“The compound exhibited anti-tumor properties in both human samples, which were outside the body, and in samples that were administered by injection into the mice,” Hyder said. “In both cases, the proteins that cause tumors to grow were eliminated, leading to more aggressive cell death.”
Hyder believes that further clinical testing can lead to a drug that has the dual purpose of fighting high cholesterol and cancer.
For more information:
Liang Y, Besch-Williford C, Aebi JD, Mafuvadze B, Cook MT, Zou X, Hyder SM.Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents: suppression of hormone-dependent breast cancer by the oxidosqualene cyclase inhibitor RO 48-8071. Breast Cancer Res Treat. 2014 May 31.[Article]]PubMed]
Photo: Salman M. Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center at the University of Missouri, Columbia, MO. Hyder proved that a compound initially developed as a cholesterol-fighting molecule not only halts the progression of breast cancer, but also can kill the cancerous cells. Photo Courtesy: University of Missouri-Columbia.
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