Mechanistic Studies of the Anticancer Activity of An Octahedral Hexanuclear Pt(II) Cage.
Yao-Rong ZhengKogularamanan SuntharalingamPeter M BrunoWei LinWeixue WangMichael T HemannStephen J LippardPublished in: Inorganica chimica acta (2016)
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.
Keyphrases
- dna damage
- endothelial cells
- circulating tumor
- oxidative stress
- cell free
- single molecule
- papillary thyroid
- dna repair
- cell death
- photodynamic therapy
- dendritic cells
- cell cycle arrest
- regulatory t cells
- induced pluripotent stem cells
- squamous cell
- case control
- young adults
- stress induced
- solid phase extraction
- signaling pathway