New Treatments in Renal Cancer: The AhR Ligands.
AhR
aminoflavone
benzothiazoles
nanocompounds
renal cancer
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 May 2020
18 May 2020
Historique:
received:
01
04
2020
revised:
30
04
2020
accepted:
05
05
2020
entrez:
24
5
2020
pubmed:
24
5
2020
medline:
26
2
2021
Statut:
epublish
Résumé
Kidney cancer rapidly acquires resistance to antiangiogenic agents, such as sunitinib, developing an aggressive migratory phenotype (facilitated by c-Metsignal transduction). The Aryl hydrocarbon receptor (AhR) has recently been postulated as a molecular target for cancer treatment. Currently, there are two antitumor agent AhR ligands, with activity against renal cancer, that have been tested clinically: aminoflavone (AFP 464, NSC710464) and the benzothiazole (5F 203) prodrug Phortress. Our studies investigated the action of AFP 464, the aminoflavone pro-drug currently used in clinical trials, and 5F 203 on renal cancer cells, specifically examining their effects on cell cycle progression, apoptosis and cell migration. Both compounds caused cell cycle arrest and apoptosis but only 5F 203 potently inhibited the migration of TK-10, Caki-1 and SN12C cells as well as the migration signal transduction cascade, involving c-Met signaling, in TK-10 cells. Current investigations are focused on the development of nano-delivery vehicles, apoferritin-encapsulated benzothiazoles 5F 203 and GW610, for the treatment of renal cancer. These compounds have shown improved antitumor effects against TK-10 cells in vitro at lower concentrations compared with a naked agent.
Identifiants
pubmed: 32443455
pii: ijms21103551
doi: 10.3390/ijms21103551
pmc: PMC7279047
pii:
doi:
Substances chimiques
AHR protein, human
0
Antineoplastic Agents
0
Basic Helix-Loop-Helix Transcription Factors
0
Benzothiazoles
0
Flavonoids
0
Ligands
0
Receptors, Aryl Hydrocarbon
0
aminoflavone
2EXS38428U
benzothiazole
G5BW2593EP
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Consejo Nacional de Investigaciones Científicas y Técnicas
ID : PIP 0812. 2014-2016
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