@Article{096504019X15517850319579,
AUTHOR = {Hyun-Jung Moon,1
 So-Young Park,1
 Su-Hoon Lee, Chi-Dug Kang, Sun-Hee Kim},
TITLE = {Nonsteroidal Anti-inflammatory Drugs Sensitize CD44-Overexpressing Cancer  Cells to Hsp90 Inhibitor Through Autophagy Activation},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {7},
PAGES = {835--847},
URL = {http://www.techscience.com/or/v27n7/48613},
ISSN = {1555-3906},
ABSTRACT = {Recently, novel therapeutic strategies have been designed with the aim of killing cancer stem-like cells (CSCs), 
and considerable interest has been generated in the development of specific therapies that target stemnessrelated marker of CSCs. In this study, nonsteroidal anti-inflammatory drugs (NSAIDs) significantly potentiated Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-mediated cytotoxicity through 
apoptotic and autophagic cell death induction, but COX-2-inhibitory function was not required for NSAIDinduced autophagy in CD44-overexpressing human chronic myeloid leukemia K562 (CD44<sup>high</sup>K562) cells.
Importantly, we found that treatment with NSAIDs resulted in a dose-dependent increase in LC3-II level and 
decrease in p62 level and simultaneous reduction in multiple stemness-related markers including CD44, Oct4, 
c-Myc, and mutant p53 (mutp53) in CD44<sup>high</sup>K562 cells, suggesting that NSAIDs could induce autophagy, 
which might mediate degradation of stemness-related marker proteins. Activation of AMPK and inhibition 
of Akt/mTOR/p70S6K/4EBP1 participated in NSAID-induced autophagy in CD44<sup>high</sup>K562 cells. In addition, 
treatment of CD44<sup>high</sup>K562 cells with NSAIDs inhibited expression of HSF1/Hsps, which resulted in suppression of 17-AAG-induced activation of Hsp70, leading to reversal of 17-AAG resistance and sensitization of 
CD44<sup>high</sup>K562 cells to 17-AAG by NSAIDs. In conclusion, combining NSAIDs with Hsp90 inhibitor may offer 
one of the most promising strategies for eradication of CD44-overexpressing CSCs.},
DOI = {10.3727/096504019X15517850319579}
}