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.
Keywords: Nelfinavir; endoplasmic reticulum stress; renal cancer; tumor necrosis factor-related apoptosis-inducing ligand.
Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.