Osteosarcoma Stem Cell Potent Gallium(III)-Polypyridyl Complexes Bearing Diflunisal.
Chemistry
; 27(55): 13846-13854, 2021 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-34269487
ABSTRACT
We report the anti-osteosarcoma stem cell (OSC) properties of a series of gallium(III)-polypyridyl complexes (5-7) containing diflunisal, a non-steroidal anti-inflammatory drug. The most effective complex within the series, 6 (containing 3,4,7,8-tetramethyl-1,10-phenanthroline), displayed similar potency towards bulk osteosarcoma cells and OSCs, in the nanomolar range. Remarkably, 6 exhibited significantly higher monolayer and sarcosphere OSC potency (up to three orders of magnitude) than clinically approved drugs used in frontline (cisplatin and doxorubicin) and secondary (etoposide, ifosfamide, and carboplatin) osteosarcoma treatments. Mechanistic studies show that 6 downregulates cyclooxygenase-2 (COX-2) and kills osteosarcoma cells in a COX-2 dependent manner. Furthermore, 6 induces genomic DNA damage and caspase-dependent apoptosis. To the best of our knowledge, 6 is the first metal complex to kill osteosarcoma cells by simultaneously inhibiting COX-2 and damaging nuclear DNA.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Óseas
/
Osteosarcoma
/
Diflunisal
/
Galio
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Chemistry
Asunto de la revista:
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido