Arowosegbe Michael Aderibigbe, Ogunleye Adewale Joseph, Eniafe Gabriel O, Omotuyi Olaposi Idowu, Ehima Victoria Obiajuru, Metibemu Damilohun Samuel, Ogungbe Bimpe, Kanmodi Rahmon Ilesanmi and Ogunmola Oluwafemi Jude
Matrix metalloproteinases, MMP-8 and MMP-13, play crucial roles in the prognosis of colorectal cancer (CRC). Although some literatures consider MMP-8 as a double-edged sword, based on its ambiguous effects in tumouriogenesis. A conglomeration of evidence has revealed that MMP-8 and MMP-13 are requisite in the degradation and remodelling of components of the extracellular matrix in colorectal cancer progression. Therefore, it is apposite to timely inhibit these Zn-dependent endopeptidases, thereby repressing the angiogenic, invasive and metastatic potentials of CRC. Early MMP inhibitors failed clinic trials due to poor oral bioavailability, metabolic instability and dose-limiting toxicity, poor trial design and the use of inadequate clinical end-points. Hence, in the current study, our aim was to source for a potent inhibitor of MMP-8 and -13 that can later scale the hurdle of drug trials. We employed in-silico approach to investigate therapeutic properties of fisetin as well as its molecular interaction in the catalytic domain of MMP-8 and -13. Fisetin partly distorts the S1 sites of the endopeptidases while partially maintaining the hydrophobic pockets. Consequently, this may explain the improved inhibition of MMP-8 and MMP-13 as compared with the standard co-crystallised inhibitors. The results from this study corroborate other findings, indicating that fisetin is probable potent anticancer drug and it can significantly palliate CRC invasion and metastasis.
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