10.1021/acs.jmedchem.9b00489.s002
Hana Kostrhunova
Hana
Kostrhunova
Juraj Zajac
Juraj
Zajac
Vojtech Novohradsky
Vojtech
Novohradsky
Jana Kasparkova
Jana
Kasparkova
Jaroslav Malina
Jaroslav
Malina
Janice R. Aldrich-Wright
Janice R.
Aldrich-Wright
Emanuele Petruzzella
Emanuele
Petruzzella
Roman Sirota
Roman
Sirota
Dan Gibson
Dan
Gibson
Viktor Brabec
Viktor
Brabec
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
American Chemical Society
2019
cytoskeleton networks
cancer cells
Pt
Microtubule Cytoskeleton
platinum agent
derivative
New Platinum Antitumor Agents Kills Cells
mechanism
platinum cytostatics
DNA
Multimodal Mechanism
5 act
triple-negative breast cancer cells MDA-MB -231.
cytotoxic metallodrug
mitochondrial membrane
multimodal MoA
contrast
2019-04-28 00:00:00
Dataset
https://acs.figshare.com/articles/dataset/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/8101166
The substitution
inert platinum agent [Pt(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)]<sup>2+</sup> (56MeSS, <b>5</b>) is a potent cytotoxic metallodrug.
In contrast to conventional cisplatin or oxaliplatin, the mechanism
of action (MoA) of <b>5</b> is fundamentally different. However,
details of the mechanism by which the 5,6-dimethyl-1,10-phenanthroline
ligand contributes to the cytotoxicity of <b>5</b> and its derivatives
have not been sufficiently clarified so far. Here, we show that <b>5</b> and its Pt(IV) derivatives exhibit an intriguing potency
in the triple-negative breast cancer cells MDA-MB-231. Moreover, we
show that the Pt(IV) derivatives of <b>5</b> act by multimodal
MoA resulting in the global biological effects, that is, they damage
nuclear DNA, reduce the mitochondrial membrane potential, induce the
epigenetic processes, and last but not least, the data provide evidence
that changes in the organization of cytoskeleton networks are functionally
important for <b>5</b> and its derivatives, in contrast to clinically
used platinum cytostatics, to kill cancer cells.