title: An in vitro and in vivo investigation of the cytotoxic effects of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester and bortezomib in multiple myeloma cells.
abstract: OBJECTIVE
  In this study, the in vitro and in vivo effectiveness of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) in combination with bortezomib, a proteasome inhibitor, was explored in multiple myeloma (MM) cells.
  
  
  METHODS
  The cytotoxic effects of CAPE and bortezomib were determined by XTT cell proliferation assay. Apoptosis levels were analyzed with annexin V-fluorescein isothiocyanate, nuclear factor kappa beta (NF-κB) was analyzed with electrophoretic mobility-shift assay, and interleukin (IL)-6 levels were analyzed with enzyme-linked immunosorbent assay to evaluate CAPE's mechanism of action. To investigate the in vivo effectiveness of CAPE and bortezomib, an experimental plasmacytoma model was induced in BALB/c mice.
  
  
  RESULTS
  Increasing concentrations of CAPE and bortezomib decreased the proliferation of ARH-77 cells in a dose-dependent manner. With doses of CAPE IC50, a significant increase in apoptosis and a significant decrease in IL-6 levels were detected. The NF-κB DNA- binding activity decreased compared to the basal ARH-77 level. The administration of CAPE alone or in combination with bortezomib increased the rate of survival compared to the control group.
  
  
  CONCLUSIONS
  We think that our study, which is the first to demonstrate the in vitro and in vivo effectiveness of the.combined use of CAPE and bortezomib, will be a pioneer for future human applications of CAPE in MM.
authors: Ertan
authors: E
authors: Altayli
authors: Özgür
authors: Ö
authors: Koru
authors: Önder
authors: Ö
authors: Öngörü
authors: Tayfun
authors: T
authors: İde
authors: Cengizhan
authors: C
authors: Açikel
authors: Meral
authors: M
authors: Sarper
authors: Mualla Pınar
authors: MP
authors: Elçi
authors: Rahşan
authors: R
authors: Ilikçi Sağkan
authors: Erhan
authors: E
authors: Astarci
authors: Duran
authors: D
authors: Tok
authors: Salim
authors: S
authors: Özenç
authors: Ali Uğur
authors: AU
authors: Ural
authors: Ferit
authors: F
authors: Avcu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002109:Caffeic Acids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma; D016328:NF-kappa B / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D002109:Caffeic Acids; D015850:Interleukin-6; D016328:NF-kappa B; D011719:Pyrazines; D000069286:Bortezomib; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol