@Article{096504016X14666990347635,
AUTHOR = {Makoto Isono, Akinori Sato, Kazuki Okubo, Takako Asano, Tomohiko Asano},
TITLE = {Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum  Stress and Histone Acetylation in Renal Cancer Cells},
JOURNAL = {Oncology Research},
VOLUME = {24},
YEAR = {2016},
NUMBER = {5},
PAGES = {327--335},
URL = {http://www.techscience.com/or/v24n5/56981},
ISSN = {1555-3906},
ABSTRACT = {The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human 
immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only increases unfolded proteins by 
suppressing HSP90 but also acts as a proteasome inhibitor. We thought that belinostat and ritonavir together 
would induce endoplasmic reticulum (ER) stress and kill renal cancer cells effectively. The combination of 
belinostat and ritonavir induced drastic apoptosis and inhibited the growth of renal cancer cells synergistically. 
Mechanistically, the combination caused ER stress (evidenced by the increased expression of the ER stress 
markers) and also enhanced histone acetylation by decreasing the expression of HDACs. To our knowledge, 
this is the first study that showed a beneficial combined effect of belinostat and ritonavir in renal cancer cells, 
providing a framework for testing the combination in renal cancer patients.},
DOI = {10.3727/096504016X14666990347635}
}