Stabilization of c-myc G-Quadruplex DNA, inhibition of telomerase activity, disruption of mitochondrial functions and tumor cell apoptosis by platinum(II) complex with 9-amino-oxoisoaporphine.
Eur J Med Chem
; 124: 417-427, 2016 Nov 29.
Article
en En
| MEDLINE
| ID: mdl-27597417
ABSTRACT
[Pd(L)(DMSO)Cl2] (1) and [Pt(L)(DMSO)Cl2] (2) with 9-amino-oxoisoaporphine (L), were synthesized and characterized. 1 and 2 are more selectively cytotoxic to Hep-G2 cells versus normal liver cells (HL-7702). Various experiments showed that 2 acted as telomerase inhibitors targeting G4-DNA and triggered cell apoptosis by interacting with c-myc G4-DNA. Furthermore, 2 significantly induced cell cycle arrest at both G2/M and S phase, which leading to the down-regulation of cdc25 A, cyclin D, cyclin B, cyclin A and CDK2 and the up-regulation of p53, p27, p21,chk1 and chk2. In addition, 2 also caused mitochondrial dysfunction. Taken together, we found that 2 exerted its cytotoxic activity mainly via inhibiting telomerase by interaction with c-myc G4-DNA and disruption of mitochondrial function.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Compuestos Organometálicos
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ADN
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Proteínas Proto-Oncogénicas c-myc
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Apoptosis
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Telomerasa
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G-Cuádruplex
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Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2016
Tipo del documento:
Article