Abstract
The discovery of the anticancer activity of cisplatin and its clinical application has opened a new field for studying metal-coordinated anticancer drugs. Metal-based anticancer drugs, such as cisplatin, can be transported to cells after entering into the human body and form metal–DNA or metal–protein adducts. Then, responding proteins will recognize adducts and form stable complexes. The proteins that were binding with metal-based anticancer drugs were relevant to their mechanism of action. Herein, investigation of the recognition between metal-based anticancer drugs and its binding partners will further our understanding about the pharmacology of cytotoxic anticancer drugs and help optimize the structure of anticancer drugs. The “soft” ionization mass spectrometric methods have many advantages such as high sensitivity and low sample consumption, which are suitable for the analyses of complex biological samples. Thus, MS has become a powerful tool for the identification of proteins binding or responding to metal-based anticancer drugs. In this review, we focused on the mass spectrometry-based quantitative strategy for the identification of proteins specifically responding or binding to metal-based anticancer drugs, ultimately elucidating their mechanism of action.
Highlights
Introduction to MetalBased Anticancer DrugsAs early as the 1960s, Rosenerg first discovered that platinum complexes have an inhibitory effect on tumor cell growth, and used platinum complexes to treat tumors [1]
Metal-based anticancer drugs have played an important role in the clinical combined with affinity chromatography, mass spectrometry-based proteomics, and bioinformatics chemotherapy of cancer, especially platinum-based anticancer drugs represented by cisplatin
The were utilized to figure out the target proteins of antimetastatic agent RAPTA in ovarian cancer adverse effects and acquired resistance of platinum-based anticancer drugs triggered researchers to lysate [50]
Summary
As early as the 1960s, Rosenerg first discovered that platinum complexes have an inhibitory effect on tumor cell growth, and used platinum complexes to treat tumors [1]. Cisplatin, oxaliplatin, and carboplatin are used worldwide as anticancer drugs. All of the clinically used platinum drugs contain a single PtII center with two exchangeable ligands in cis geometry. The interaction of these drugs with cellular biomolecules such as sulfur-containing glutathione and metallothionein can deactivate them before reaching their pharmacological target, DNA [2,3]. Studies have suggested that transplatin is inactive, but recent studies have found that some trans-platinum complexes have good in vitro and in vivo anti-tumor activity. 2019,drugs, 24, 581 several proteins/enzymes have recently been proposed to be involved in the action anticancer of platinum complexes [16]
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