Ghazala Muteeb

Cancer incidence varies around the globe, implying a relationship between food and cancer risk. Plant polyphenols are a class of secondary metabolites that have recently attracted attention as possible anticancer agents. The subclass of polyphenols, known as isoflavones, includes genistein and daidzein, which are present in soybeans and are regarded as potent chemopreventive agents. According to epidemiological studies, those who eat soy have a lower risk of developing certain cancers. Several mechanisms for the anticancer effects of isoflavones have been proposed, but none are conclusive. We show that isoflavones suppress prostate cancer cell growth by mobilizing endogenous copper. The copper-specific chelator neocuproine decreases the apoptotic potential of isoflavones, whereas the iron and zinc chelators desferroxamine mesylate and histidine do not, confirming the role of copper. Reactive oxygen species (ROS) scavengers reduce isoflavone-induced apoptosis in these cells, implying that ROS are cell death effectors. Our research also clearly shows that isoflavones interfere with the expression of the two copper transporter genes, CTR1 and ATP7A, in cancerous cells. Copper levels are widely known to be significantly raised in all malignancies, and we confirm that isoflavones can target endogenous copper, causing prooxidant signaling and, eventually, cell death. These results highlight the importance of copper dynamics within cancer cells and provide new insight into the potential of isoflavones as cancer-fighting nutraceuticals.

Bioassay-guided isolation from Camellia sinensis (Theaceae) and Colchicum luteum (Liliaceae) utilizing an in vitro model of protease assay revealed colchicine (1) and caffeine (2) from chloroform fractions, respectively. Their structures were validated using spectral techniques. The purified compounds were further optimized with Gaussian software utilizing the B3LYP functional and 6-31G(d,p) basis set. The result files were utilized to determine several global reactivity characteristics to explain the diverse behavior of the compounds. Colchicine (1) showed a higher inhibition of protease activity (63.7 ± 0.5 %age with IC50 = 0.83 ± 0.07 mM), compared with caffeine (2) (39.2 ± 1.3 %age). In order to determine the type of inhibition, compound 1 was further studied, and, based on Lineweaver–Burk/Dixon plots and their secondary replots, it was depicted that compound 1 was a non-competitive inhibitor of this enzyme, with a Ki value of 0.690 ± 0.09 mM. To elucidate the theoretical features of protease inhibition, molecular docking studies were performed against serine protease (PDB #1S0Q), which demonstrated that compound 1 had a strong interaction with the different amino acid residues located on the active site of this understudied enzyme, with a high docking score of 16.2 kcal/mol.