Label-Free Bioelectrochemical Methods for Evaluation of Anticancer Drug Effects at a Molecular Level

Abstract

Cancer is a multifactorial family of diseases that is still a leading cause of death worldwide. More than 100 different types of cancer affecting over 60 human organs are known. Chemotherapy plays a central role for treating cancer. The development of new anticancer drugs or new uses for existing drugs is an exciting and increasing research area. This is particularly important since drug resistance and side effects can limit the efficacy of the chemotherapy. Thus, there is a need for multiplexed, cost-effective, rapid, and novel screening methods that can help to elucidate the mechanism of the action of anticancer drugs and the identification of novel drug candidates. This review focuses on different label-free bioelectrochemical approaches, in particular, impedance-based methods, the solid supported membranes technique, and the DNA-based electrochemical sensor, that can be used to evaluate the effects of anticancer drugs on nucleic acids, membrane transporters, and living cells. Some relevant examples of anticancer drug interactions are presented which demonstrate the usefulness of such methods for the characterization of the mechanism of action of anticancer drugs that are targeted against various biomolecules.

Targeting the Copper Transport System to Improve Treatment Efficacies of Platinum-Containing Drugs in Cancer Chemotherapy

“…This methodology, while it did not directly measure Pt drug transport in living cells because of the limitations mentioned, it provided valuable information that otherwise would not be available. These results implicate that the gross mechanisms of Pt(II) transport by ATP7A and ATP7B are similar to the Cu(I) transport [55].…”

Stimulation of Ca2+‐ATPase Transport Activity by a Small‐Molecule Drug

“…In particular, the SSM method has successfully been employed to evaluate the effects of pharmacologically relevant compounds on P-type ATPases. [29] The mechanisms of interaction of various inhibitory compounds with SERCA were investigated using the SSM method. [13] The present research aims at investigating the stimulatory effect of the compound CDN1163 on the transport activity of the SERCA enzyme.…”

Protein Adsorption on Solid Supported Membranes: Monitoring the Transport Activity of P-Type ATPases

“…It has been shown that drug/protein interactions can be conveniently monitored on SSMs. In particular, the SSM technique has demonstrated its usefulness to investigate the effects of various pharmaceutically relevant compounds on P-type ATPases [ 29 , 33 , 111 ], which are important targets for a variety of drugs [ 112 , 113 , 114 ]. Therefore, this technique represents a robust and reliable assay in drug development and evaluation studies on membrane transport proteins, as it can be used to quantify the effectiveness and potency of drugs directed toward specific protein targets, and to characterize novel drug candidates.…”

“…Finally, the SSM technique has been successfully employed to evaluate the effects of pharmacologically relevant compounds, such as anti-cancer drugs [ 33 ], on the transport activity of P-type ATPases and to characterize the interaction of specific ATPase inhibitors, thereby providing a quantitative estimate of inhibition potency (IC 50 values).…”