Cisplatin To Blame For Zinc Deficiency

New findings about the way the anticancer drug cisplatin binds to the common blood protein albumin may explain how cisplatin causes zinc deficiency in chemotherapy patients. Cisplatin, which is widely used to treat ovarian, testicular, bladder, head, and other solid tumors, is believed to kill cancer cells primarily by binding to DNA. It also binds to albumin, but the mechanism of that binding interaction has never been fully characterized. Now, a group has used tryptic digestion, liquid chromatography, and tandem mass spectrometry to identify the sites on albumin where cisplatin binds (Chem. Commun., DOI: 10.1039/c1cc11627d). The study was carried out by Fuyi Wang of the Chinese Academy of Sciences, in Beijing; Peter J. Sadler of the University of Warwick, in England; and coworkers. It shows that cisplatin cross-links two key histidines on albumin, thus blocking the protein’s major zinc-binding site. The researchers believe this interaction may account for the zinc deficiency in blood and excessive zinc in urine observed in some cisplatin-treated patients. The work could help lead to cisplatin analogs that lessen or eliminate these side effects.