Exploring the anti-metastatic potential of sunitinib and novel analogs in colorectal cancer: insights into HIF-1α mediated metastasis

Computational analyses highlighted the importance of HIF-1α as a crucial mediator of metastasis in CRC. Molecular docking and dynamics simulations demonstrated favorable and stable interaction of sunitinib and three novel analogs with HIF-1α PAS-B domain. Volcano plots indicated upregulation of <i>HIF1A</i> in LoVo cells compared to six other CRC cell lines. Findings of <i>in vitro</i> studies revealed considerable inhibitory effects of sunitinib and analogs on LoVo cell migration and invasion in hypoxic condition. Gelatin zymography and qPCR analysis indicated decreased activity of MMP-2 and MMP-9, along with downregulation of EMT transcription factors in hypoxic condition. Current study reports promising anti-metastatic effects of sunitinib and novel analogs on CRC cells, providing foundation for further investigation to combat cancer metastasis.