Piperlongumine inhibits cell growth and enhances TRAIL-induced apoptosis in prostate cancer cells

• Published in: Asian Pacific Journal of Tropical Biomedicine
• Main Authors: Gorkem Kismali, Ahmet Ceylan, Ogunc Meral, Merve Alpay, Funda Kosova, Dilek Ulker Cakir, Begum Yurdakok-Dikmen, Neslihan Tascene, Tevhide Sel
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wolters Kluwer Medknow Publications 2020
• Subjects: piperlongumine; prostate cancer; apoptosis; tumor necrosis factor-related apoptosis-inducing ligand; Arctic medicine. Tropical medicine; RC955-962; Biology (General); QH301-705.5; Arctic
• Online Access: https://doi.org/10.4103/2221-1691.281465; https://doaj.org/article/599d2cc38da94c908bdab4ff66c07b86

Objective: To investigate whether piperlongumine can sensitize prostate cancer cells to tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) and trigger apoptosis in prostate cells. Methods: Human prostate cancer cell lines PC3, LNCaP, and VCaP were cultured with piperlongumine and TRAIL. Then, cell proliferation, migration, caspase activation, apoptotic protein expressions, and death receptor expressions were measured. Results: Piperlongumine inhibited cell proliferation at low doses (<10 μM) alone and in combination with TRAIL (25 ng/mL), induced apoptosis, and suppressed cyclooxygenase activation. Additionally, piperlongumine induced expression of death receptors which potentiated TRAIL-induced apoptosis in cancer cells but did not affect decoy receptors. Piperlongumine also downregulated tumor cell-survival pathways, inhibited colony formation and migration of cancer cells alone or in combination with TRAIL. The combination of piperlongumine with TRAIL was found to be synergistic. Conclusions: Our findings indicate that piperlongumine can sensitize cancer cells to TRAIL through the upregulation of death receptors and can trigger apoptosis with the downregulation of anti- apoptotic proteins.