Monitoring the mechanism of anti-cancer agents to inhibit colorectal cancer cell proliferation: Enzymatic biosensing of glucose combined with molecular docking.

Glucose, a major energy source in cellular metabolism, has a significant role in cell growth. The increase in glucose uptake is a distinguishing hallmark in cancer cells. A key step in glucose utilization is the transport of glucose to the cancer cells for supplying their additional energy. The glucose transporter (or GLUT) family is a membrane protein which facilitates the uptake of glucose in most cancer cell types. Given the increased glucose level in cancer cells and the regulatory role of GLUTs in glucose uptake, it is required to combine both experimental and theoretical studies to develop new methods to monitor cell proliferation. Herein, for the first time, a new strategy was proposed to evaluate the cell proliferation of HT-29 based on glucose consumption in the presence of resveratrol (RSV) as an anticancer agent. A hybrid nanocomposite of carbon nanofibers and nitrogen-doped graphene quantum dots was used to design an enzymatic sensor for the selective and sensitive determination of glucose in cancer cells. The results obtained from the voltammetric technique were compared with the conventional colorimetric assay. A good correlation was observed between the proliferation rate and glucose utilization by cancer cells. As it was observed, RSV induces a decrease in glucose consumption, indicating lower glucose uptake efficiency for HT-29 cells. Molecular docking studies reveal that RSV can block the interaction of glucose with the GLUT family. This is one of the possible mechanisms for the decrease of glucose level followed by the reduction of cell proliferation in the presence of RSV. Compared with traditional methods, in vitro electrochemical techniques benefit from simple, nontoxic, sensitive and low-cost detection assays and hence serve as a novel tool to pursue the growth inhibition of cancer cell in response to anti-cancer agents.