Stearic acid (stearate) is an 18-carbon saturated fatty acid that has been shown to inhibit invasion and proliferation stearate and induce apoptosis in various human cell types. The specificity of stearate-induced apoptosis on cancerous versus non-cancerous breast cells has not been examined, and the underlying mechanism of stearate-induced apoptosis is unclear. Morphological analysis, cell viability, and caspase-3 activity assays demonstrated that stearate preferentially activates apoptosis in cancer cells in a time- and dose-dependent manner. Inhibition of de novo diacylglycerol synthesis or protein kinase C (PKC) blocks stearate-induced caspase-3 activity, suggesting the involvement of a novel or classical PKC isozyme. To our knowledge, this is the first study to show that stearate preferentially induces apoptosis in breast cancer cells and involves protein kinase C in the signaling cascade. These results raise the possibility that dietary stearate may play a beneficial role in the prevention or treatment of breast cancer.
Stearic acid (stearate) is an 18-carbon saturated fatty acid that is relatively high in several foods in the Western diet, including beef and chocolate. In vitro and in vivo studies suggest that stearate may have unique properties, especially with regard to breast cancer development and tumor progression. For example, stearate has been shown to inhibit epidermal growth factor (EGF) receptor-mediated proliferation of Hs578t breast cancer cells (1), inhibit invasion of HT-1080 fibrosarcoma cells (2), and induce MDA-MB- 231 breast cancer cells apoptotic cancer cells (3). In vivo, dietary stearate is associated with reduced breast tumor development and incidence in spontaneous carcinogenic models (4, 5). A recent meta-analysis of 13 studies compared human erythrocyte membrane, serum, and adipocyte fatty acid composition in relation to breast cancer risk (6). This study found that stearate was associated with a reduced risk of breast cancer in postmenopausal women but was not associated with breast cancer risk in the remaining cohort (6). A recent case-control study in Shanghai, China also reported that stearate was not associated with breast cancer risk (7). These results suggest that dietary stearate can reduce or have no effect on breast cancer risk in humans. Taken together, in vitro, in vivo, and epidemiological studies suggest that stearate has the potential to prevent and treat breast cancer; however, little is known about the mechanism of action of stearate, including its induction of apoptosis.