Light-inducible control of cellular proliferation and differentiation by a Hedgehog signaling inhibitor

The Hedgehog (Hh) signaling pathway is a major regulator of cell differentiation and proliferation. Aberrant activation of the Hh pathway has been implicated in several types of cancer. To understand the Hedgehog pathway and fight against related diseases, it is important to inhibit Hedgehog signaling in a targeted manner. However, no tools are available for the precise inhibition of Hh signaling in a spatiotemporal manner. In this study, we synthesized and evaluated the bioactivity of a light-inducible Hh pathway inhibitor (NVOC-SANT-75). NVOC-SANT-75 inhibits transcription factor Gli1 in NIH3T3 cells and controls proliferation and differentiation of primary cultured mouse cerebellar neurons in a light-irradiation-dependent manner. The light-inducible Hedgehog signaling inhibitors may be a new candidate for light-mediated cancer treatment.