Inhibition of the Inositol Requiring Protein 1α- X-Box Binding Protein-1 Pathway as a Promising Therapeutic Target for Human Prostate Cancer

Ahmad M. Khalil^1, , Ahmad Y. Alghadi¹, Rahaf M. T. Shahen¹, Jehad W. Elasad² and Khaleel I. Jawasreh³

¹Department of Biological Sciences, Yarmouk University, Irbid, Jordan

²Department of Applied Biology, Jordan University of Science and Technology, Irbid, Jordan

³Department of Animal Productions, Jordan University of Science and Technology, Irbid, Jordan

Cite this paper:
Ahmad M. Khalil, Ahmad Y. Alghadi, Rahaf M. T. Shahen, Jehad W. Elasad and Khaleel I. Jawasreh. Inhibition of the Inositol Requiring Protein 1α- X-Box Binding Protein-1 Pathway as a Promising Therapeutic Target for Human Prostate Cancer. Journal of Cancer Research and Treatment. 2018; 6(3):74-79. doi: 10.12691/jcrt-6-3-3

Abstract

Prostate cancer (PCa) has been associated with endoplasmic reticulum stress (ERS) which activates the inositol requiring protein 1α- X-box binding protein-1 (IREα-XBP-1) pathway. The aim of the study was to investigate the role of this pathway in three human PCa cell lines (LNCaP, PC-3, and DU-145) by evaluating the expression of XBP-1 and glucose-regulated protein 78 (GRP78) genes. The effect of two ERS inducers (Thapsigargin, Tg and tunicamycin, Tm) alone and in combination with an inhibitor of the IRE1α RNase inhibitor (STF-083010) on expression profiling was followed using Quantitative-PCR. In vitro treatment of PCa cells with ERS inducers upregulated expression of XBP-1 gene. STF-083010 inhibited IRE1α-induced splicing of the gene and increased cytotoxicity. Inhibition of IRE1α RNase activity significantly decreased expression of chaperon protein GRP78. The results confirm and extend the concept that selective targeting of IRE1α-XBP-1 pathway might be a novel therapeutic approach that curbs PCa cell progression.

Keywords:
ER stress GRP78 IRE1 α-XBP-1 pathway prostate cancer STF-083010 unfolded protein response

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