Akinori Sato, Takako Asano, Kazuki Okubo, Makoto Isono, Tomohiko Asano

Oncology Research, Vol.26, No.2, pp. 323-332, 2018, DOI:10.3727/096504017X14957929842972

Abstract The human immunodeficiency virus (HIV) protease inhibitor nelfinavir acts against malignancies by inducing endoplasmic reticulum (ER) stress. The HIV protease inhibitor ritonavir, on the other hand, not only induces ER stress but also inhibits P-glycoprotein’s pump activity and thereby enhances the effects of its substrate drugs. We therefore postulated that ritonavir in combination with nelfinavir would kill bladder cancer cells effectively by inducing ER stress cooperatively and also enhancing nelfinavir’s effect. Nelfinavir was shown to be a P-glycoprotein substrate, and the combination of nelfinavir and ritonavir inhibited bladder cancer cell growth synergistically. It also suppressed… More >

Makoto Isono, Akinori Sato, Kazuki Okubo, Takako Asano, Tomohiko Asano

Oncology Research, Vol.24, No.5, pp. 327-335, 2016, DOI:10.3727/096504016X14666990347635

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 More >