Anti-proliferative and metastatic protease inhibitory activities of protoberberines: An in silico and in vitro approaches

• High binding affinity of alkaloids with metastatic proteases by in silico study.
• Proliferation and metastasis inhibitory activity of alkaloids on cancer cell lines.
• Protoberberine alkaloids exhibits high therapeutic potential against cancer cells.

In metastasis, tumour cells interact with numerous factors and one of them is extracellular matrix (ECM). Earlier studies have emphasised the on role of matrix metalloproteases (MMPs) and cathepsin B in ECM degradation and cancer metastasis. In silico docking approaches are a boon in exploring the physicochemical characteristics like angiogenesis, growth and repair of cancerous cells. The binding affinities of berberrubine, jatrorrhizine and thalifendine with caspase 3, MMP-9, cathepsin B and telomeric DNA were performed using hex 6v and iGEMDOCK v2.1 software tools. The present investigation on berberrubine, jatrorrhizine and thalifendine revealed the formation of potentially stable complexes with caspase 3, cathepsin B and telomeric DNA similar to doxorubicin, a well-known anticancer drug. Further, in vitro approaches were made to study anti-proliferative activity against colon, lymphoma and ovarian cancer cell lines and enzyme inhibition activity against MMP-9 and cathepsin B. The results obtained reveal that these protoberberines alkaloids have potential inhibitory effect on cancer cell proliferation as well as metastatic proteases.