Regulation of Hedgehog Signaling in Cancer by Natural and Dietary Compounds

The aberrant Hedgehog (Hh) signaling induced by mutations or overexpression of the signaling mediators has been implicated in cancer, associated with processes including inflammation, tumor cell growth, invasion and metastasis, as well as cancer stemness. Small molecules targeting the regulatory components of the Hh signaling pathway, especially Smoothened (Smo), have been developed for the treatment of cancer. However, acquired resistance to a Smo inhibitor vismodegib observed in clinical trials suggests that other Hh signaling components need to be explored as potential anticancer targets. Natural and dietary compounds provide a resource for the development of potent agents affecting intracellular signaling cascades, and numerous studies have been conducted to evaluate the efficacy of natural products in targeting the Hh signaling pathway. In this review, we summarize the role of Hh signaling in tumorigenesis, discuss results from recent studies investigating the effect of natural products and dietary components on Hh signaling in cancer, and provide insight on novel small molecules as potential Hh signaling inhibitors.