Down-Regulation of NRF2 Signaling Triggers Cell Death in Y79 Cells upon Copper Chelation

Authors: Aloysius Dhivya M , Kishore A and Bharathidevi SR*

DOI: 10.23880/oajo-16000329

Volume 10, Issue 1

Abstract

Background: Retinoblastoma is a rare intraocular malignancy that leads to vision loss in children. While copper (Cu) chelation has been reported as a therapy in many cancers, its relevance to retinoblastoma has not yet been explored. Objectives: In this study, we have explored the role of penicillamine (a Cu chelator) as a therapeutic target for retinoblastoma using Y79 cells as a model. Methods: The effect of the Cu chelator on the viability of Y79 was assessed using the MTT assay. Additionally, we performed nuclear fractionation to assess Nuclear factor erythroid 2–related factor 2 (NRF2) activation, evaluated the downstream targets of NRF2 at transcript and protein levels, and measured SOD (superoxide dismutase) activity. Results: Penicillamine (2 mM) induced cell death in Y79 cells, inhibited NRF2 signaling, and reduced SOD activity. Furthermore, the downstream targets of NRF2 namely VEGF as well as PCNA (proliferating cell nuclear antigen) were decreased with penicillamine, which induced cell death in Y79 cells. We observed similar results in HeLa cells (positive control) comparable to Y79 cells. Conclusion: Therefore, we speculate that penicillamine could be a target for retinoblastoma as it induces cell death in Y79 cells by regulating NRF2 nuclear translocation and decreasing its downstream targets.

Keywords: Retinoblastoma; Y79; Penicillamine; Copper Chelation; NRF2

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