A novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cells.
J Inorg Biochem
; 190: 45-66, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30352315
ABSTRACT
A novel binuclear Cd complex (1) with hydrazone-based ligand was prepared and characterized by spectroscopy and single crystal X-ray diffraction techniques. Complex 1 reveals a strong pro-apoptotic activity in both human, mammary adenocarcinoma cells (MCF-7) and pancreatic AsPC-1 cancer stem cells (CSCs). While apoptosis undergoes mostly caspase-independent, 1 stimulates the activation of intrinsic pathway with noteworthy down regulation of caspase-8 activity in respect to non-treated controls. Distribution of cells over mitotic division indicates that 1 caused DNA damage in both cell lines, which is confirmed in DNA interaction studies. Compared to 1, cisplatin (CDDP) does not achieve cell death in 2D cultured AsPC-1 cells, while induces different pattern of cell cycle changes and caspase activation in 2D cultured MCF-7 cells, implying that these two compounds do not share similar mechanism of action. Additionally, 1 acts as a powerful inducer of mitochondrial superoxide production with dissipated trans-membrane potential in the majority of the treated cells already after 6â¯h of incubation. On 3D tumors, 1 displays a superior activity against CSC model, and at 100⯵M induces disintegration of spheroids within 2â¯days of incubation. Fluorescence spectroscopy, along with molecular docking show that compound 1 binds to the minor groove of DNA. Compound 1 binds to the human serum albumin (HSA) showing that the HSA can effectively transport and store 1 in the human body. Thus, our current study strongly supports further investigations on antitumor activity of 1 as a drug candidate for the treatment of highly resistant pancreatic cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias Pancreáticas
/
Células Madre Neoplásicas
/
Cadmio
/
Complejos de Coordinación
/
Hidrazonas
Límite:
Humans
Idioma:
En
Revista:
J Inorg Biochem
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia