Is the dinner plate an answer to cancer metastasis?

Abstract

There is increasing evidence that the manifestation of cancer is controlled in part by environmental events. In addition to events that result in oncogenic mutations (such as smoking or radiation exposure), lifestyle activities, such as diet and exercise, have an impact on cancer through mechanisms that have yet to be explained. My laboratory has examined the nature of cancer regulation by specific phytochemicals found in a nutritious vegetable diet and the way in which they impact cancer. Specifically, sulforaphane, found in cruciferous vegetables such as broccoli, reduces cancer incidence in animal models. A broccoli-rich diet in humans is associated with reduced cancer mortality. We sought to identify possible protein targets of sulforaphane using a biotin-conjugated sulforaphane homologue. Unexpectedly, we found that the cytokine MIF (macrophage migration inhibitory factor) is covalently modified by sulforaphane. Genetic depletion of MIF in murine 4T1 breast cancer cells had no effect on growth in vitro or on tumour growth in immunodeficient animals. However, when grown in genetically matched BALB/c mice, MIF-deficient tumour cells grew slowly and entirely failed to display pulmonary metastasis. Treatment of animals bearing MIF-normal tumours with sulforaphane resulted in a similar reduction in tumour growth and suppression of metastasis. A mechanism for suppression of metastatic growth of tumours has been published recently by collaborators (Simpson, Templeton and Cross, Journal of Immunology, 2012), which involves a reduction in tumour-induced myeloid-derived suppressor cells (MDSCs). The idea that anticancer phytochemicals may suppress the growth and metastasis of cancer cells rather than their initiation has been underexplored. Our findings support the notion that post-therapy cancer patients may benefit by long-term consumption of normal or high amounts of foods containing cancer-suppressing phytochemicals such as sulforaphane.