Four Novel Rho-associated Coiled-coil Protein Kinase 1 Inhibitors Suppressing Cytoskeleton and Movement in Breast...

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Rho-associated coiled-coil protein kinase 1 (ROCK1) is a crucial regulator of cellular processes and implicated in various diseases.
• ROCK1 plays a significant role in cellular metabolism, growth, differentiation, and signaling pathways.

Purpose of the Study:

• To identify novel inhibitors of ROCK1.
• To evaluate the efficacy of identified ROCK1 inhibitors against MDA-MB-231 breast cancer cells.

Main Methods:

• Virtual screening and enzymatic activity assays were employed to identify ROCK1 inhibitors.
• Cell proliferation, cytoskeletal organization, migration, and invasion assays were performed using MDA-MB-231 cells.

Main Results:

• Four novel ROCK1 inhibitors (bilobetin, SCH 772984, puerarin 6''-O-xyloside, and GSK 650394) were identified with IC50 values ranging from 11.82 to 18.09 µM.
• These compounds inhibited breast cancer cell proliferation (IC50: 20-32 µM) and reduced EdU uptake.
• ROCK1 inhibition led to cytoskeletal disruption, impairing cell migration (70%-85% inhibition) and invasion (69%-86% inhibition).

Conclusions:

• The identified compounds are potent ROCK1 inhibitors with significant anti-breast cancer activity.
• These novel molecular scaffolds offer potential for developing new anti-breast cancer therapeutics.