Gli pathway-targeted Co(iii) Schiff base complexes inhibit migration of basal cell carcinoma cells

Abstract

Basal Cell Carcinoma (BCC) is the most frequently diagnosed cancer globally and affects about one in five Americans. Given the frequency of diagnosis, it is surprising that there are very few therapeutic options. Surgical removal is currently the most common treatment option; however, this can lead to noticeable scarring and cosmetic issues. As a result, there is a compelling interest in developing non-invasive therapeutic approaches to this disease. Here, we introduce a new transition metal–DNA derivative called CoGli–GOPEI that inhibits the migration of murine ASZ BCC cells in laboratory experiments. Notably, this complex significantly outperforms two established hedgehog-pathway inhibitors: GANT-61 (an investigational compound) and vismodegib (an FDA-approved drug). These inhibitors target the hedgehog signaling pathway—specifically the Gli family of transcription factors—to slow cancer progression. By effectively reducing cell migration, CoGli–GOPEI offers a less invasive alternative to traditional treatments like surgical resection and chemotherapy. Our results highlight how targeting the Gli transcription factors within the hedgehog pathway can create a novel therapeutic strategy against BCC. The ultimate goal of these new derivates is to reduce the spread of cancer cells while minimizing the downsides of surgery.