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Herbal Medicine Gamma-Linolenic Acid Boosts the Effectiveness of Herceptin in Cancer Cells

EVANSTON, IL -- November 3, 2005 -- Gamma-linolenic acid (GLA), which is found in several plant oils and is used in herbal medicine, appears to be able to prevent resistance to the breast cancer drug Herceptin, according to a report in the Journal of the National Cancer Institute (JNCI).

Researchers at the Evanston Northwestern Healthcare (ENH) Research Institute examined the effect of GLA on the expression of the cancer gene Her-2/neu, and discovered that GLA kills cancer cells without affecting normal cells.

Researchers treated cancer cells with GLA and discovered that GLA treatment substantially reduced Her-2/neu protein levels in breast, ovarian and gastrointestinal cancers. Additionally, concurrent treatments of Her-2/neu overexpressing cancer cells with GLA and Herceptin led to synergistic increases in cell death and reduced growth and colony formation.

"The Her-2/neu oncogene plays a crucial role not only in the origin and progression of numerous types of human cancer but also in their responses to various treatments," said Ruth Lupu, PhD, Director of Translational Breast Cancer Research at the ENH Research Institute. "These findings reveal a valuable means by which an inexpensive herbal medicine might regulate cancer cell growth, metastasis, and sensitivity to chemo and endocrine therapies."

Patients with cancer that exhibit high levels of Her-2/neu generally have a low survival rate. Treatments that target Her-2/neu in cancer cells, such as the drug Herceptin, have been shown to be useful. However, fewer than 35 percent of patients with Her-2/neu-overexpressing metastatic breast cancer respond to Herceptin alone. Furthermore, the majority of patients who initially respond to Herceptin acquire resistance within one year. So finding the mechanisms of resistance to Herceptin can help in the development of new compounds that might overcome resistance or have synergistic antitumor effects when given with Herceptin.

"In our tests, treating the cancer cell lines with both GLA and Herceptin led to a synergistic increase in cell death and reduced cancer cell growth," said Dr. Lupu. "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."

"GLA's inhibition of Her-2/neu works in a different manner from that of Herceptin," said co-researcher Javier A. Menendez, PhD, research scientist Evanston Northwestern Research Institute. "While Herceptin attempts to neutralize thousands of Her-2/neu molecules commonly found in overexpressing cancer cells, GLA would be more efficient to reduce Her-2/neu levels by preventing the gene from copying itself."

Lupu and Menendez were also the researchers who discovered that the oleic acid found in olive oil dramatically reduces the levels of a protein produced by the breast cancer gene Her-2/neu.

The latest study was supported by funding from the Susan G. Komen Breast Cancer Foundation and the federal government.

REFERENCE:
Effect of Gamma-Linolenic Acid on the Transcriptional activity of the Her- 2/neu (erbB-2) oncogene. Journal of the National Cancer Institute, Vol. 97, No. 21, November 2, 2005, p. 1611-1615.


SOURCE: Evanston Northwestern Healthcare

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