Analysis\nof Antiangiogenic Potential and Cell Death\nMechanism of a Kinetically Inert Platinum Antitumor Agent

Cancer is a multifaceted disease\ninvolving various pathological\nprocesses, including uncontrolled proliferation, development of resistance,\nangiogenesis, metastasis, etc. Therefore, chemotherapeutic agents\ncapable of simultaneously inhibiting proliferation, circumventing\nchemoresistance, and inhibiting angiogenesis can address multiple\naspects of cancer progression. We recently identified a highly promising\nkinetically inert platinum antitumor agent, namely, <b>Pt-1</b>, that can circumvent cisplatin resistance and showed negligible\nnephrotoxicity. In this study, we explored the antiangiogenic potential\nand elucidated the detailed mechanism of cell death through which\nit exerts its antitumor activity. <b>Pt-1</b> strongly inhibited\nangiogenesis in a zebrafish <i>in vivo</i> model at its\ntherapeutically relevant nontoxic dose. Further, <b>Pt-1</b> exerted antitumor activity through necroptosis- and paraptosis-mediated\ncell death. Taken together, the combination of antitumor activity\nwith antiangiogenic property in <b>Pt-1</b> makes it a highly\npromising antitumor candidate.