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.
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
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