A ruthenium(II) complex inhibits tumor growth in vivo with fewer side-effects compared with cisplatin

Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct‐[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine], by in vitro and in vivo assays

“…These erythrocytes have a relatively short lifespan so that any micronucleus is the result of recently induced chromosome damage (Hayashi et al, ). Taken together, the results suggest that the compound studied does not induce genotoxicity in healthy tissues and that its mechanism of action differs from that of cisplatin, confirming the lower toxic effects of ruthenium compounds compared to cisplatin reported in the literature (Haghdoost et al, ; Van Rijt & Sadler, ; Wang et al, ).The in vivo comet assay has the advantage that it allows the identification of possible DNA damage in different organs of the animal, and that it is sensitive to the detection of low degrees of DNA damage (Hayashi et al, ). The comet assay for the detection of genotoxic effects is usually performed in the liver, which is the main organ for the metabolic activation of substances after systemic exposure (Rothfuss et al, ).…”

“…The different doses of ct ‐[RuCl(CO)(dppb)(bipy)]PF 6 and of the positive controls were administered intraperitoneally. This route of administration was chosen based on studies of in vivo antitumor activity with metal compounds (Bergamo et al, ; Menezes et al, ; Wang et al, ). Bone marrow and hepatocyte samples were collected 24 hours after treatment for the micronucleus and comet assays, respectively.…”

A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition

“…Furthermore, we note several structurally-related RPCs have been shown to induce DNA-damage independent apoptosis in cancer cell lines, where a common finding is the induction of mitochondrial dysfunction and accompanying ROS-generation161718192021. In clear contrast to these studies, we find 1 inhibits cancer cell growth by Chk1-mediated G1-S cell-cycle arrest, where prolonged Chk1 pathway activation is in agreement with activation of the replication checkpoint stabilising stalled replication forks339.…”

“…While the majority of ruthenium-based anticancer compounds owe their effects to their reactivity and formation of coordinate (irreversible) bonds with DNA in a similar manner to cisplatin15, there has been growing interest in the bioactivity of RPCs that bind DNA solely by intercalation9. Although several RPC metallo-intercalators have been shown to inhibit cancer cell proliferation in vitro and in vivo 161718192021, there are surprisingly few examples implying DNA binding is responsible for bioactivity2223. Moreover, the impact of RPC intercalation on DNA replication and the cellular response to induced DNA damage are completely unexplored.…”

A cyclometalated iridium(III) complex that inhibits the migration and invasion of MDA-MB-231 cells

“…Fortunately, research on transition metal-based drugs offers hope in the fight against breast cancer. For instance, two ruthenium(III) compounds, NAMI-A and KP1019, have successfully entered clinical trials due to its ability to combat the development of solid tumor metastasis [4]. Other types of transition metal complexes should be evaluated to determine if they possess similar anticancer properties.…”