Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin increases the activation of aryl hydrocarbon receptor and is associated with the aggressiveness of osteosarcoma MG-63 osteoblast-like cells

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics and physiological ligands. Activation of the AhR by environmental xenobiotics may induce a conformational change in AhR and has been implicated in a variety of cellular processes, including inflammation and tumorigenesis. It is unknown whether the activation of AhR serves a role in modulating the progression of osteosarcoma. The osteosarcoma cell line MG-63, was treated with AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD treatment degrades AhR expression through activation of the AhR signaling pathway, however there were no survival differences observed in MG-63 cells. There were concomitant elevations of cyclooxygenase-2 and receptor activator of nuclear factor-κB ligand secretion from MG-63 cells upon TCDD treatment on a protein and mRNA level at 24 and 72 h. In addition, TCDD treatment also increases the production of prostaglandin E2 on MG-63 cells, and induces the expression of chemokine receptor CXCR4. However, CXCL12 production was not altered in MG-63 cells when stimulated with TCDD. The AhR antagonist CH-223191, blocks the effects on TCDD-induced RANKL, COX-2, PGE2 and CXCR4 changes. In conclusion, these findings suggest that AhR signal therapy should be further explored as a therapeutic option for the treatment of osteosarcoma.

Reoxygenation induces reactive oxygen species production and ferroptosis in renal tubular epithelial cells by activating aryl hydrocarbon receptor

“…In the present study, reoxygenation decreased AhR levels. The decrease in AhR level indicates its activation since activated AhR becomes vulnerable to proteasomal degradation, leading to decreased AhR cellular levels (20)(21)(22)(23)(24). Accordingly, reoxygenation increased the expression of CYP1A1, an AhR transcriptional target (18,19).…”

“…When activated by exogenous or endogenous ligands, AhR is released, translocates into the nucleus, forms a complex with HIF-1β, and transcribes the CYPs CYP1A1, CYP1A2, and CYP1B1 (18,19). Interestingly, activated AhR becomes vulnerable to proteasomal degradation, leading to decreased AhR cellular levels (20)(21)(22)(23)(24).…”

Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells

“…The reoxygenation-induced kynurenine-overproduction was accompanied by a reduction in AhR levels. Reduction in AhR levels reflects the activation status of the receptor as only the activated form of AhR is targeted by proteasomal degradation leading to decreased AhR cellular levels (20,21). Under the reoxygenation conditions, both 1-MT, which by inhibiting IDO prevents kynurenine production (7,8,15), and CH223192, which inhibits AhR directly (16), prevented AhR activation (Fig.…”

Phycocyanin from Arthrospira platensis as Potential Anti-Cancer Drug: Review of In Vitro and In Vivo Studies

“…In MDA-MB-231 breast cancer cells, actin filaments were reduced while the migration potential decreased with PC supplementation [ 65 ]. PC is an inhibitor of cyclooxygenase 2 (COX-2), which converts arachidonic acid to prostaglandins and plays a key role in tumor progression and chemical resistance [ 71 , 72 , 73 ]. Prostaglandin-E2 is a tightly regulated product of COX-2, which promotes angiogenesis [ 74 , 75 ].…”