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Gli pathway-targeted Co(iii) Schiff base complexes inhibit migration of basal cell carcinoma cells
Caroline E Bond1, Keaton D Olson1, Metehan Punar1
1Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University Evanston IL USA tmeade@northwestern.edu.
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.
Insights
A new compound, CoGli-GOPEI, effectively inhibits Basal Cell Carcinoma (BCC) cell migration, offering a promising, less invasive therapeutic alternative to surgery.
Area of Science:
- Oncology
- Biochemistry
- Materials Science
Background:
- Basal Cell Carcinoma (BCC) is the most common cancer globally, yet therapeutic options are limited, often involving surgery with cosmetic side effects.
- There is a significant need for non-invasive treatments for BCC.
- Targeting the hedgehog signaling pathway, particularly Gli transcription factors, is a key strategy in BCC treatment.
Purpose of the Study:
- To introduce and evaluate a novel transition metal-DNA derivative, CoGli-GOPEI, as a potential non-invasive therapeutic agent for Basal Cell Carcinoma (BCC).
- To compare the efficacy of CoGli-GOPEI against established hedgehog pathway inhibitors in inhibiting BCC cell migration.
Main Methods:
- Development of a novel transition metal-DNA derivative, CoGli-GOPEI.
- In vitro laboratory experiments using murine ASZ BCC cells.
- Comparative analysis of CoGli-GOPEI against GANT-61 and vismodegib, known hedgehog pathway inhibitors.
Main Results:
- CoGli-GOPEI demonstrated significant inhibition of murine ASZ BCC cell migration in laboratory experiments.
- The compound outperformed two established hedgehog pathway inhibitors, GANT-61 and vismodegib, in inhibiting cell migration.
- These findings suggest CoGli-GOPEI's potential as a novel therapeutic strategy.
Conclusions:
- CoGli-GOPEI represents a promising novel therapeutic agent for Basal Cell Carcinoma (BCC) by inhibiting cancer cell migration.
- Targeting Gli transcription factors within the hedgehog pathway offers a viable strategy for developing less invasive BCC treatments.
- The development of CoGli-GOPEI could lead to reduced cancer spread with fewer side effects than traditional therapies.
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