Inhibition of Glutaredoxin 5 predisposes Cisplatin-resistant Head and Neck Cancer Cells to Ferroptosis.

Theranostics
Jaewang LeeJong-Lyel Roh

Abstract

Rationale: Loss of iron-sulfur cluster function predisposes cancer cells to ferroptosis by upregulating iron-starvation response, but the role of glutaredoxin 5 (GLRX5) silencing in ferroptosis remains unknown. We examined the role of GLRX5 functional loss in promoting ferroptosis in cisplatin-resistant head and neck cancer (HNC) cells. Methods: The effects of sulfasalazine treatment and GLRX5 gene silencing were tested on HNC cell lines and mouse tumor xenograft models. These effects were analyzed concerning cell viability and death, lipid reactive oxygen species (ROS) and mitochondrial iron production, labile iron pool, mRNA/protein expression, and malondialdehyde assays. Results: Cyst(e)ine deprivation, erastin, or sulfasalazine induced ferroptosis in HNC cells, which was relatively less sensitive in cisplatin-resistant HNC cells. Sulfasalazine or cyst(e)ine deprivation-induced ferroptosis resulted from increased lipid peroxidation and intracellular free iron, which were significantly promoted by short-interfering RNA or short hairpin RNA (shRNA) targeting GLRX5 (P<0.05). GLRX5 silencing activated iron-starvation response and boosted up intracellular free iron through the iron-responsive element-binding activity of increased...Continue Reading

Citations

Sep 13, 2020·Journal of Experimental Botany·Ayelén Mariana DistéfanoGabriela Carolina Pagnussat
Apr 6, 2021·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Fang HanZhanqiu Wang
Nov 21, 2020·Cell Metabolism·Jiashuo Zheng, Marcus Conrad
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sepideh MirzaeiKwang-Seok Ahn
May 2, 2021·Clinical and Translational Medicine·Zheng TangNitao Cheng
Jun 4, 2021·Journal of Ovarian Research·Mingyang Zhu, Shiqi Xiao
Jun 29, 2021·Frontiers in Cell and Developmental Biology·Hui WangAnwen Shao

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