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
| Autor: | V. Olivares-Illana, I. Alvarado-Morales, Claudia Escudero-Lourdes, E. Reynaga-Hernández, E.J. Tokar, E. Layseca-Espinosa, C. Arenas-Huertero |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Genotype Population Apoptosis Toxicology Article Cancer stem cell Humans Receptor education Cells Cultured Aged Aged 80 and over Toll-like receptor education.field_of_study Chemistry Toll-Like Receptors Prostate Genetic Variation Prostatic Neoplasms Epithelial Cells General Medicine Middle Aged Sodium Compounds Retinoic acid receptor Cell Transformation Neoplastic Cell culture Cancer research Neoplastic Stem Cells Stem cell |
| Zdroj: | Toxicol Lett |
| ISSN: | 1879-3169 |
| Popis: | 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. Polyinosinic:polycytidylic acid (PIC) is a Toll-like receptor 3 (TLR3) agonist that induces tumor cells apoptosis after activation. PIC+9cRA combination activates retinoic acid receptor β (RARβ) 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 RARβ expression, on As-CSC and iAs-transformed epithelial cells (CAsE-PE). As-CSCs and CAsE-PE showed lower TLR3 and RARβ 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 RARβ 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect