Selenium–Platinum Coordination Compounds as Novel Anticancer Drugs: Selectively Killing Cancer Cells via a Reactive Oxygen Species (ROS)‐Mediated Apoptosis Route

Abstract

We report the preparation of selenium-containing platinum-based anticancer drug EG-Se/Pt. EG-Se/Pt was obtained from the coordination of selenium-containing molecules (EG-Se) with cisplatin (CDDP). The structure of EG-Se/Pt was characterized by (1) H and (77) Se NMR spectroscopy, XPS, ESI-MS, and MALDI-TOF. In aqueous solution, EG-Se/Pt self-assembles to form spherical aggregates. EG-Se/Pt shows enhanced stability against dilution and high salt concentration compared with EG-Se. EG-Se/Pt induces cell apoptosis via reactive oxygen species (ROS), which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays. More importantly, EG-Se/Pt effectively inhibits tumor growth in vivo in tumor-bearing mice. It is anticipated that tuning the ROS level through the assembly of selenium-containing molecules can be a general method to realize anticancer selectivity.

Selenium–Platinum Coordination Dendrimers with Controlled Anti-Cancer Activity

“…35 2) Selenium as well as other potential ligands on selenium-containing molecules replaces both chloro and amino ligands of cisplatin, leading to the inactivation of the active site and the formation of a selenium−platinum active site. 39,40 MALDI-TOF results supported the second hypothesis ( Figure 2). For the complex of the first generation dendrimer and cisplatin, the main peak at m/z 884.…”

Effect of oxaliplatin combined with polyenephosphatidylcholine on the proliferation of human gastric cancer SGC-7901 cells

“…It has been reported that platinum causes mitochondrial dysfunction, possibly by inhibiting the electron transfer system, resulting in the increased production of hydrogen peroxide, superoxide anions and hydroxyl radicals (18,27), which generate reactive oxygen species (ROS) (28). The majority of cells in the body contain enzymes that act as antioxidants and remove ROS (19,29).…”

“…This inhibition leads to the release of cytochrome c , which triggers the apoptosis of cancer cells (26,38). During this process, cytochrome c activates caspases 9 and 3, with the help of apoptotic protease-activating factor 1 (27,39), and activated caspase 3 subsequently suppresses caspase-activated DNase, inducing DNA fragmentation (28,40). The present study suggested that L-OHP may activate this apoptotic pathway in mitochondria, where it functions primarily by inducing DNA fragmentation and chromatin condensation.…”

Treatment with a selenium-platinum compound induced T-cell acute lymphoblastic leukemia/lymphoma cells apoptosis through the mitochondrial signaling pathway

“…Se-containing compounds are able to induce tumor cell cycle arrest and apoptosis, through the expression of cyclin-dependent kinase inhibitor 1A and 1B, the inhibition of PKB, extracellular-signal-regulated kinase 1/2 and JNK1/2, and the generation of reactive oxygen species (ROS) (9,10). Certain Se-based compounds are able to selectively kill cancer cells in vitro and in vivo (11,12). ROS have been reported to induce apoptosis via a series of downstream signaling pathways including a mitochondrial cascade (13,14).…”

“…ROS have been reported to induce apoptosis via a series of downstream signaling pathways including a mitochondrial cascade (13,14). Furthermore, increased ROS levels in cancer cells serve a role in the selective killing of cancer cells by antitumor agents (12,15). Chemists from Tsinghua University (Beijing, China) have developed a novel compound, EG-Se/Pt, based on the coordination of Se-containing small molecules (EG-Se) and CDDP, which demonstrates broad-spectrum anticancer activity in breast, lung and liver cancer cell lines, and selectivity of tumor cells (12).…”