Tumor Cell-selective Synergism of TRAIL- and ATRA-induced Cytotoxicity in Breast Cancer Cells.
Anticancer Res
; 38(5): 2669-2682, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-29715087
ABSTRACT
BACKGROUND/AIM:
One of the major problems in breast cancer treatment is pharmacoresistance. Therefore, exploration of treatment alternatives is of clinical relevance. The present work focused on tumor cell-inhibiting effects of a combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and all trans retinoic acid (ATRA) in breast cancer cells. MATERIALS ANDMETHODS:
Breast cancer cell lines (BT-20, BT-474, MDA-MB-231, MDA-MB-436, MDA-MB-453, MCF-7, SKBR3, T47D, ZR-75-1) and the mammary epithelial cell line MCF-10A were treated with TRAIL and ATRA alone and in combination. Cell viability was assessed via 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay, the potential of cell colony formation via clonogenic assay, cell death induction via cell-cycle analysis by fluorescence-activated cell sorting (FACS), terminal deoxynucleotidyltransferase-mediated UTP nick end labeling (TUNEL) assay and Cell death detection ELISAPLUS, expression of apoptosis and TRAIL pathway proteins via western blot and cell surface expression of TRAIL receptor 1 (DR4) via FACS analysis.RESULTS:
TRAIL and ATRA evoked synergistic inhibition of breast cancer cell viability based on cytostatic and cytotoxic mechanisms. This correlated with augmented fragmentation of nuclear DNA, up-regulation of TRAIL receptor, down-regulation of cyclin D1 and enhancement of caspase activity. MCF-10A cells were merely slightly susceptible to TRAIL and ATRA.CONCLUSION:
The cytostatic and cytotoxic effects of the combination of TRAIL and ATRA are tumor cell-selective.Palabras clave
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Neoplasias de la Mama
/
Ligando Inductor de Apoptosis Relacionado con TNF
Límite:
Female
/
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
GR
/
GRECIA
/
GREECE
/
GRÉCIA