PT  - JOURNAL ARTICLE
AU  - OKUBO, KAZUKI
AU  - SATO, AKINORI
AU  - ISONO, MAKOTO
AU  - ASANO, TAKAKO
AU  - ASANO, TOMOHIKO
TI  - Nelfinavir Induces Endoplasmic Reticulum Stress and Sensitizes Renal Cancer Cells to TRAIL
AID  - 10.21873/anticanres.12754
DP  - 2018 Aug 01
TA  - Anticancer Research
PG  - 4505--4514
VI  - 38
IP  - 8
4099  - http://ar.iiarjournals.org/content/38/8/4505.short
4100  - http://ar.iiarjournals.org/content/38/8/4505.full
SO  - Anticancer Res2018 Aug 01; 38
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.