Mechanistic studies of the anticancer activity of an octahedral hexanuclear Pt(II) cage

This study provides an in-depth mechanistic investigation of the origin of antiproliferative activity for a self-assembled platinum cage. Unlike classical platinum-based anticancer agents, this construct interacts with DNA in a non-covalent, intercalative manner and promotes DNA condensation. [Displ...

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Bibliographic Details
Published in:Inorganica Chimica Acta 2016-10, Vol.452, p.125-129
Main Authors: Zheng, Yao-Rong, Suntharalingam, Kogularamanan, Bruno, Peter M., Lin, Wei, Wang, Weixue, Hemann, Michael T., Lippard, Stephen J.
Format: Article
Language:English
Subjects:
Anticancer
Anticancer properties
Apoptosis
Cage
Cages
Cancer
Deoxyribonucleic acid
DNA
DNA damage
Ligands
Phosphorylation
Platinum
Prescription drugs
Self-assembly
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Summary:This study provides an in-depth mechanistic investigation of the origin of antiproliferative activity for a self-assembled platinum cage. Unlike classical platinum-based anticancer agents, this construct interacts with DNA in a non-covalent, intercalative manner and promotes DNA condensation. [Display omitted] •A hexanuclear platinum cage has anti-proliferative effects against human cancer cells.•Unlike classical Pt anticancer agents, this cage interacts with DNA non-covalently.•The cage intercalates into DNA and promotes DNA condensation.•In cancer cells, the cage induces DNA damage and triggers apoptosis and senescence. The cellular response evoked by a hexanuclear platinum complex, Pt6L4 (1), is reported. Compound 1, a 3-nm octahedral cage formed by self-assembly of six Pt(II) centers and four 2,4,6-tris(4-pyridyl)-1,3,5-triazine ligands (L), exhibits promising in vitro potency against a panel of human cancer cell lines. Unlike classical platinum-based anticancer agents, 1 interacts with DNA in a non-covalent, intercalative manner and promotes DNA condensation. In cancer cells, 1 induces DNA damage, upregulates p53, its phosphorylated form phospho-p53 and its downstream effector, p21, as well as both apoptosis and senescence.
ISSN:0020-1693
1873-3255
DOI:10.1016/j.ica.2016.03.021