Data from Auranofin Protects Intestine against Radiation Injury by Modulating p53/p21 Pathway and Radiosensitizes Human Colon Tumor

• DOI: 10.1158/1078-0432.c.6527657.v1
• Publication Date: 2023-04-01T06:25:14Z
• Authors: Dhrubajyoti Nag; Payel Bhanja; Randal Riha; Giselle Sanchez-G...; Bruce F. Kimler; Terance T. Tsue; Chris Lominska; Subhrajit Saha
• Keywords: Auranofin; Radiosensitivity; Organoid

<div>AbstractPurpose:<p>The radiosensitivity of the normal intestinal epithelium is major limiting factor for definitive radiotherapy against abdominal malignancies. Radiosensitizers, which can be used without augmenting radiation toxicity to tissue, are still an unmet need. Inhibition proteosomal degradation being developed as a therapeutic strategy anticancer therapy cancer cells more susceptible proteasomal inhibition–induced cytotoxicity compared with cells. Auranofin, gold-containing antirheumatoid drug, blocks by inhibiting deubiquitinase inhibitors. In this study, we have examined whether auranofin selectively radiosensitizes colon tumors promoting in intestine.</p>Experimental Design:<p>The effect (10 mg/kg i.p.) on response subcutaneous CT26 and gastrointestinal was determined using mouse model radiation. The also paired human colonic organoid system malignant nonmalignant tissues from same patient.</p>Results:<p>Both injury culture, pretreatment prevented improved survival activation p53/p21–mediated reversible cell-cycle arrest. However, tumor organoids, inhibited tissue growth inhibition degradation, induction endoplasmic reticulum stress/unfolded protein response, apoptosis.</p>Conclusions:<p>Our data suggest that potential candidate considered combination improve efficacy malignancies.</p></div>