Human prostate epithelial cells and prostate-derived stem cells malignantly transformed in vitro with sodium arsenite show impaired Toll like receptor -3 (TLR3)-associated anti-tumor pathway.
Toxicol Lett
; 350: 185-193, 2021 Oct 10.
Article
en En
| MEDLINE
| ID: mdl-34303791
ABSTRACT
A therapeutic strategy for prostate cancer (PCa) involves the use of 9-cis-retinoic acid (9cRA) to induce cancer stem cells (CSCs) differentiation and apoptosis. Polyinosinicpolycytidylic acid (PIC) is a Toll-like receptor 3 (TLR3) agonist that induces tumor cells apoptosis after activation. PIC+9cRA combination activates retinoic acid receptor ß (RARß) re-expression, leading to CSC differentiation and growth arrest. Since inorganic arsenic (iAs) targets prostatic stem cells (SCs), we hypothesized that arsenic-transformed SCs (As-CSCs) show an impaired TLR3-associated anti-tumor pathway and, therefore, are unresponsive to PIC activation. We evaluated TLR3-mediated activation of anti-tumor pathway based in RARß expression, on As-CSC and iAs-transformed epithelial cells (CAsE-PE). As-CSCs and CAsE-PE showed lower TLR3 and RARß basal expression compared to their respective isogenic controls WPE-Stem and RWPE-1. Also, iAs transformants showed reduced expression of mediators in TLR3 pathway. Importantly, As-CSCs were irresponsive to PIC+9cRA in terms of increased RARß and decreased SC-markers expression, while CAsE-PE, a heterogeneous cell line having a small SC population, were partially responsive. These observations indicate that iAs can impair TLR3 expression and anti-tumor pathway activated by PIC+9cRA in SCs and prostatic epithelial cells. These findings suggest that TLR3-activation based therapy may be an ineffective therapeutic alternative for iAs-associated PCa.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Células Madre Neoplásicas
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Compuestos de Sodio
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Células Epiteliales
/
Receptores Toll-Like
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Aged
/
Aged80
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Toxicol Lett
Año:
2021
Tipo del documento:
Article
País de afiliación:
México