Gamma-linolenic acid (GLA), a substance in evening primrose oil and several other plant oils used in herbal medicine, inhibits action of Her-2/neu, a cancer gene that is responsible for almost 30 percent of all breast cancers, Northwestern University researchers report.
"Breast cancer patients with Her-2/neu-positive tumors have an aggressive form of the disease and a poor prognosis," said Ruth Lupu, director of Evanston Northwestern Healthcare Breast Cancer Translational Research Program, who led the study, published in the Nov. 2 issue of the Journal of the National Cancer Institute.
Lupu is professor of medicine at Northwestern University Feinberg School of Medicine and a researcher at The Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Lupu and co-investigator Javier Menendez showed that treating cancer cells that overexpressed Her-2/neu with GLA not only suppressed protein levels of the oncogene, but also caused a 30- to 40-fold increased response in breast cancer cells to the drug HerpetinTM (trastuzumab), a monoclonal antibody that is used for the treatment of many women with breast cancer.
Menendez is research assistant professor of medicine at Feinberg and a scientist at Evanston Northwestern Healthcare Research Institute.
"In our tests, treating the cancer cell lines with both GLA and Herceptin led to a synergistic increase in apoptosis [cell death] and reduced cancer growth. Therefore, although further studies are necessary before GLA can enter clinical trials, these findings may reveal a previously unrecognized way of influencing the poor outcome of Her-2/neu-positive cancer patients," Lupu said. "GLA's inhibition of Her-2/neu works in a different manner from that of Herceptin," Menendez said.
"While Herceptin attempts to neutralize thousands of Her-2/neu molecules commonly found in the surface of overexpressing cancer cells, GLA would be more efficient to reduce Her-2/neu levels by preventing the transcription of few Her-2/neu gene copies," Menendez said. "Considering that activation and overexpression of the Her-2/neu oncogene are crucial events in the cause, progression and cell sensitivity to various treatments in breast cancer, results of the study showed reveal a valuable means by which an inexpensive herbal medicine might regulate might regulate breast cancer cell growth, metastasis formation and response to chemotherapies and endocrine therapies," Lupu said.
GLA exerts selective toxic effects on cancer cells without affecting normal cells. Menendez's earlier research showed that supplementation with GLA sensitizes breast cancer cells to some chemotherapeutic drugs, such as paclitaxel (TaxolTM), docetaxel (TaxotereTM) and vinorelbine (NavelbineTM). Lupu and Menendez recently demonstrated that GLA also enhances the efficacy of anti-estrogens, such as tamoxifen and FaslodexTM.
"Since overexpression of Her-2/neu generally confers resistance to chemo- and endocrine therapies, our current findings can explain why GLA increases the efficacy of breast cancer treatments," Menendez said.
GLA is one of two essential fatty acids -- fats that are necessary for maintaining normal functioning and growth of cells, nerves, muscles and organs. Besides evening primrose oil, other sources of GLAs include borage oil and black current seed oil.
Besides Menendez, other authors on the study were Luciano Vellon, Evanston Northwestern Healthcare Research Institute; and Ramon Colomer, head of the medical oncology division at the Institut Catala d'Oncologia, Girona, Spain.
This research was supported by grant BRCTR0403141 from the Susan G. Komen Foundation and BC033538 from the Breast Cancer Program of the Department of Defense.
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