Do well-orchestrated pharmacokinetic properties of curcumin downregulate PYGB expression for glycogen phosphorylase in cancer cells?

Abstract

Abstract BACKGROUND: Metabolic reprogramming contributes energy and multiple factors in the adaption of cancer cells in nutrient-deficient conditions. In such conditions, glycogen metabolism is upregulated by the activity of glycogen phosphorylase (PYGB) to produce glucose for promoting cell proliferation as well as resistance to anticancer therapies. Hence, the present study emphasized the assessment of the pharmacokinetic properties of a natural product, curcumin, to downregulate the PYGB expression. METHODS: The pharmacokinetic properties of curcumin were performed by the admetSAR database and SwissADME web tool. Next, molecular docking of curcumin with PYGB was done by PatchDock and FireDock Server. The CABS-flex2.0 server was used for the calculation of the RMFS (root mean square fluctuation) value of PYGB. The STRING database was used for PYGB protein-interaction network (PIN) analysis. RESULTS: Curcumin followed all parameters of pharmacokinetic properties. Further, molecular docking revealed that curcumin has the potential to disrupt structural PYGB protein with binding energy (-24.62 kcal/mol). The CABS-flex2.0 server calculated the RMFS value of active sites of the docked PYGB to understand the flexibility of the interacted residues (GLU124, SER651, GLN96, LYS655, GLU121, and LYS551). The STRING database for PYGB PIN analysis suggested that other proteins like PYGL, PYGM, nuclear speckle splicing regulatory protein 1, C6orf221, and APOA1BP could also be altered by employing of curcumin. CONCLUSION: This study suggested that curcumin can alter the activity of metabolic reprogramming by targeting several factors associated with carcinogenesis in stress conditions.