2019
DOI: 10.1021/acs.jmedchem.9b00489
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A Subset of New Platinum Antitumor Agents Kills Cells by a Multimodal Mechanism of Action Also Involving Changes in the Organization of the Microtubule Cytoskeleton

Abstract: The substitution inert platinum agent [Pt(1S,2Sdiaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)] 2+ (56MeSS, 5) is a potent cytotoxic metallodrug. In contrast to conventional cisplatin or oxaliplatin, the mechanism of action (MoA) of 5 is fundamentally different. However, details of the mechanism by which the 5,6-dimethyl-1,10-phenanthroline ligand contributes to the cytotoxicity of 5 and its derivatives have not been sufficiently clarified so far. Here, we show that 5 and its Pt(IV) derivatives exhibit a… Show more

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Cited by 57 publications
(45 citation statements)
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“…Furthermore, Kostrhunova et al . found that a subset of new platinum antitumor agents kills cells in part by altering microtubule cytoskeleton organization [18]. It is therefore possible that SPC25 might promote BC development and progression by binding to microtubule proteins.…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, Kostrhunova et al . found that a subset of new platinum antitumor agents kills cells in part by altering microtubule cytoskeleton organization [18]. It is therefore possible that SPC25 might promote BC development and progression by binding to microtubule proteins.…”
Section: Discussionmentioning
confidence: 99%
“…Recently it was shown by Brabec et al that certain Pt(IV) complexes inhibit the organization of microtubule. 48 Here in, we find that oxamusplatin not only targets DNA but disrupts the organization of microtubules affecting the cytoskeleton.…”
Section: Tubulin Polymerization Inhibition Assaymentioning
confidence: 75%
“…Some previous studies have shown that tubulin plays an important role in cell cycle and cell proliferation. Many antitumor drugs kill cancer cells by changing the microstructure of cancer cells (26,27). Therefore, in the development and progression of HCC, VCAN is likely to interact with the microtubule structure to promote cancer.…”
Section: Discussionmentioning
confidence: 99%