Mechanistic Studies of the Anticancer Activity of An Octahedral Hexanuclear Pt(II) Cage.
The cellular response evoked by a hexanuclear platinum complex, Pt6L4(1), is reported. Compound1, 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,1interacts with DNA in a non-covalent, intercalative manner and promotes DNA condensation. In cancer cells,1induces DNA damage, upregulates p53, its phosphorylated form phospho-p53 and its downstream effector, p21, as well as both apoptosis and senescence.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Yao-Rong
YR
Zheng
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Kogularamanan
K
Suntharalingam
The Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Peter M
PM
Bruno
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Wei
W
Lin
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Weixue
W
Wang
The Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Michael T
MT
Hemann
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; The Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Stephen J
SJ
Lippard
Anticancer; Cage; DNA damage; Self-assembly