Piperlongumine inhibits cell growth and enhances TRAIL-induced apoptosis in prostate cancer cells
Gorkem Kismali1, Ahmet Ceylan2, Ogunc Meral1, Merve Alpay3, Funda Kosova4, Dilek Ulker Cakir5, Begum Yurdakok-Dikmen6, Neslihan Tascene7, Tevhide Sel1
1 Ankara University, Faculty of Veterinary Medicine, Department of Biochemistry, Ankara, Turkey
2 Ankara University, Faculty of Veterinary Medicine, Department of Histology and Embryology, Ankara, Turkey
3 Ankara University, Faculty of Veterinary Medicine, Department of Biochemistry, Ankara; Duzce University, Faculty of Medicine, Department of Biochemistry, Duzce, Turkey
4 Celal Bayar University, School of Health Services, Department of Biochemistry, Manisa, Turkey
5 Canakkale Onsekiz Mart University, Faculty of Medicine, Department of Medical Biochemistry, Canakkale, Turkey
6 Ankara University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Ankara, Turkey
7 Republic of Turkey Ministry of Agriculture and Forestry, Ankara, Turkey
Ankara University, Faculty of Veterinary Medicine, Department of Biochemistry, Ankara
Source of Support: This work was supported by the Turkish Scientific Council
(TUBITAK), Grant# 115S942, Conflict of Interest: None
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.