RT Journal Article
SR Electronic
T1 Nelfinavir Induces Endoplasmic Reticulum Stress and Sensitizes Renal Cancer Cells to TRAIL
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4505
OP 4514
DO 10.21873/anticanres.12754
VO 38
IS 8
A1 OKUBO, KAZUKI
A1 SATO, AKINORI
A1 ISONO, MAKOTO
A1 ASANO, TAKAKO
A1 ASANO, TOMOHIKO
YR 2018
UL http://ar.iiarjournals.org/content/38/8/4505.abstract
AB Background/Aim: Induction of endoplasmic reticulum (ER) stress is a novel strategy for cancer treatment. The human immunodeficiency virus protease inhibitor nelfinavir was recently shown to induce ER stress, but its anti-neoplastic activity has never been investigated in renal cancer, as far as we are aware. Materials and Methods: Using renal cancer cells (769-P, 786-O, Caki-2), the ability of nelfinavir to induce ER stress and sensitize them to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was tested. Results: Nelfinavir caused apoptosis and inhibited renal cancer growth in a dose-dependent fashion. It also suppressed colony formation significantly. Nelfinavir induced ER stress and increased the expression of TRAIL death receptor (DR) 4 and DR5, sensitizing the cancer cells to TRAIL. This sensitization was blocked by human recombinant DR4/Fc and DR5/Fc chimeric protein, confirming that the sensitization was due to increased expression of both DR4 and DR5. Conclusion: Nelfinavir induces ER stress in renal cancer cells and sensitizes them to TRAIL.