Chemoresistance in H-Ferritin Silenced Cells: The Role of NF-κB.
Ilenia AversaRoberta ChirilloEmanuela ChiarellaFabiana ZoleaMaddalena Di SanzoFlavia BiamonteCamillo PalmieriFrancesco CostanzoPublished in: International journal of molecular sciences (2018)
Nuclear Factor-κB (NF-κB) is frequently activated in tumor cells contributing to aggressive tumor growth and resistance to chemotherapy. Here we demonstrate that Ferritin Heavy Chain (FHC) protein expression inversely correlates with NF-κB activation in cancer cell lines. In fact, FHC silencing in K562 and SKOV3 cancer cell lines induced p65 nuclear accumulation, whereas FHC overexpression correlated with p65 nuclear depletion in the same cell lines. In FHC-silenced cells, the p65 nuclear accumulation was reverted by treatment with the reactive oxygen species (ROS) scavenger, indicating that NF-κB activation was an indirect effect of FHC on redox metabolism. Finally, FHC knock-down in K562 and SKOV3 cancer cell lines resulted in an improved cell viability following doxorubicin or cisplatin treatment, being counteracted by the transient expression of inhibitory of NF-κB, IκBα. Our results provide an additional layer of information on the complex interplay of FHC with cellular metabolism, and highlight a novel scenario of NF-κB-mediated chemoresistance triggered by the downregulation of FHC with potential therapeutic implications.
Keyphrases
- nuclear factor
- signaling pathway
- induced apoptosis
- lps induced
- pi k akt
- toll like receptor
- papillary thyroid
- oxidative stress
- cell cycle arrest
- reactive oxygen species
- squamous cell
- inflammatory response
- cell proliferation
- drug delivery
- healthcare
- diabetic rats
- lymph node metastasis
- squamous cell carcinoma
- cell death
- combination therapy
- cancer therapy
- high glucose
- young adults
- childhood cancer
- endothelial cells