Open AccessAuranofin Protects Intestine against Radiation Injury by Modulating p53/p21 Pathway and Radiosensitizes Human Colon Tumor
Author(s) -
Dhrubajyoti Nag,
Payel Bhanja,
Randal Riha,
Giselle Sánchez-Guerrero,
Bruce F. Kimler,
Terance T. Tsue,
Chris Lominska,
Subhrajit Saha
Publication year - 2019
Publication title -
clinical cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.427
H-Index - 324
eISSN - 1557-3265
pISSN - 1078-0432
DOI - 10.1158/1078-0432.ccr-18-2751
Subject(s) - auranofin , radiosensitivity , cancer research , radiation therapy , colorectal cancer , radiosensitizer , toxicity , medicine , organoid , pharmacology , cancer , biology , microbiology and biotechnology , rheumatoid arthritis
The radiosensitivity of the normal intestinal epithelium is the major limiting factor for definitive radiotherapy against abdominal malignancies. Radiosensitizers, which can be used without augmenting radiation toxicity to normal tissue, are still an unmet need. Inhibition of proteosomal degradation is being developed as a major therapeutic strategy for anticancer therapy as cancer cells are more susceptible to proteasomal inhibition-induced cytotoxicity compared with normal cells. Auranofin, a gold-containing antirheumatoid drug, blocks proteosomal degradation by inhibiting deubiquitinase inhibitors. In this study, we have examined whether auranofin selectively radiosensitizes colon tumors without promoting radiation toxicity in normal intestine.