Luca Ronconi

Preclinical activity of multiple-target gold(III)-dithiocarbamato peptidomimetics in prostate cancer cells and xenografts

BACKGROUNDnRecently, novel gold(III)-dithiocarbamato peptidomimetics, designed to target peptide transporters upregulated in several tumor cells have shown promise as anticancer agents.nnnRESULTSnThe biological behavior of the most promising derivatives AuD8 and AuD9 was studied in PC3 and DU145 prostate cancer cells. They exert higher cytotoxicity in vitro than the reference drug cisplatin and induce apoptosis, promoting mitochondrial membrane permeabilization and stimulating reactive oxygen species generation. Moreover, they inhibit both selenoenzyme thioredoxin reductase and proteasome activity. Additionally, AuD8 effectively reduces tumor growth in prostate tumor-bearing nude mice with minimal systemic toxicity.nnnCONCLUSIONnAltogether, our results provide insights into the anticancer activity of these gold(III)-dithiocarbamato peptidomimetics and support their potential as new agents for prostate cancer treatment.

A. Sigel, H. Sigel, E. Freisinger, Roland K. O. Sigel (Eds): “Metallo-drugs: development and action of anticancer agents”, volume 18 of metal ions in life sciences

If one works within the field of bioinorganic chemistry, the periodic coming out of the volume of the Sigels’ series is a recurrent event that is awaited with great interest. Although the current series started in 2006, the first volume dates back to 1973. The original idea was to disseminate the knowledge of the varied biological roles of metal ions and to promote and encourage research in the field by creating a point of reference for scientists dealing with the subject. Since then, the book series entitled Metal Ions in Biological Systems (MIBS) has provided insights into the role, biological relevance and mechanism of action of metals and metal complexes through the publication of thematic volumes focusing on different aspects of bioinorganic chemistry. This series represented the first systematic report on the state of the art in the field, ranging from the understanding of the involvement of “simple” metal ions in biological processes and their effects on the environment to the development of metallodrugs and analytical techniques to detect and quantify biologically relevant metals. Remarkably, those volumes would not be merely regarded as specialized university textbooks. In fact, the well-established and undoubted experience of the many authors that contributed over the years, in particular by including their own individual research, findings and expertise, has made the series an up-to-date fundamental reference that has supported and inspired generations of scientists and researchers. Given the impressive development and rising interest in biological inorganic chemistry during the last decades, a new series entitled Metal Ions in Life Sciences (MILS) was initiated in 2006, aimed at expanding the knowledge in the field to meet the ever-changing needs in the Life Sciences and tackle in an effective and timely way the associated challenges. Notably, the various topics have been increasingly discussed in a multidisciplinary way not only by taking into account the “chemistry and biochemistry behind” but also by including aspects of biology, physiology and medicine among others. This year’s volume, edited by Astrid Sigel, Helmut Sigel, Eva Freisinger and Roland K. O. Sigel, is the eighteenth of the MILS series and is entitled “Metallo-Drugs: Development and Action of Anticancer Agents”. As indicated in the title, the book is specifically concerned with the current status of metal-based potential chemotherapeutics and focuses on the understanding of the mode of action of metallodrugs currently under development (either in pre-clinical or in clinical trial stage). Although this subject has been already dealt with in the previous MIBS series, either comprehensively (volumes 11, 14, 41 and 42) or with reference to the medicinal properties of complexes containing specific metals (e.g., volumes 17 and 31), this is the first book of the MILS series entirely dedicated to metal-based anticancer agents. Given the ever-increasing interest and the amount of related articles published in recent years (including several dedicated review papers), this volume provides a comprehensive in-depth and timely review of such a hot topic. The book is split into 17 chapters, each dedicated to a specific class of metal derivatives, and takes advantage of the contributions of 39 authors of proven expertise in their respective subjects. A book concerning metallodrugs cannot disregard platinum-based anticancer agents. Since the approval of cisplatin for cancer chemotherapy in the early 1970s, the design of alternative, more efficient and less toxic platinum derivatives has been initially the main driving force to the development of metallodrugs. Notwithstanding the hundreds of cytotoxic platinum complexes reported to date, only three (i.e., cisplatin, carboplatin and oxaliplatin) have been approved and marketed worldwide, and their transport, mechanism of action and interaction with biomolecules are yet to be fully understood. In this regard, Chapter 1 not only summarizes * Luca Ronconi luca.ronconi@nuigalway.ie