Dietary Stearate Is an Effective Complementary Agent to Paclitaxel in Reducing the Incidence and Tumor Burden of Breast Cancer Lung Metastasis
Robert W Hardy, Gabriel Rezonzew, Xiangmin Zhao, Renee Desmond, Gene P Siegal. University of Alabama at Birmingham, Birmingham, AL
Background: Stearate is an 18-carbon saturated fatty acid found in meat and chocolate that has been shown to have anti-breast cancer properties in terms of preventing carcinogenesis and reducing tumor burdens. However dietary stearate per se does not reduce the incidence of metastasis. Paclitaxel (PTX) is a chemotherapeutic agent commonly used to treat breast cancer which has a mechanism of action that is different from that of stearate. Our hypothesis is that dietary stearate when combined with PTX will work additively or synergistically to reduce the incidence of breast cancer metastasis in a mouse model.
Design: Four diets were used in our experimental design: control (low fat) diet (5% corn oil), safflower diet (20% safflower oil), corn oil diet (17% corn oil/3% safflower oil) and stearate diet (17% stearate/3% safflower oil), n=25-30 mice per group. Diets were initiated 3 weeks prior to the injection of breast cancer cells. Female athymic nude mice were injected with 1x105 MDA-MB-435 human breast cancer cells in their mammary fat pad. The primary tumor grew to 1cm3, were removed and the mice were treated paclitaxel (20 mg/kg, IP) weekly for 3 weeks at which time the mice were sacrificed and lung tumors assessed.
Results: PTX alone decreased the incidence of lung metastasis by 50% when combined with the control diet. However dietary stearate combined with PTX significantly reduced lung metastasis another 28% (p<0.05) compared to both the control and corn oil diets. Thus the combination of dietary stearate plus PTX reduced the incidence of lung metastasis to 22% in a mouse model that has virtually a 100% incidence of lung metastasis when untreated. In addition dietary stearate reduced lung metastasis tumor burden in those mice that did develop lung metastasis (p<0.01) compared to the control diet.
Conclusions: Dietary stearate increased the effectiveness of PTX chemotherapy to prevent the incidence of lung metastasis and reduce metastasis tumor burden. Future studies will test whether using dietary stearate with chemotherapy can reduce the effective dose of PTX and thereby potentially reduce the serious side effects associated with taxanes.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 7, Tuesday Afternoon