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

作者：Altayli Ertan^*; Koru Ozgur; Ongoru Onder; Ide Tayfun; Acikel Cengizhan; Sarper Meral; Elci Mualla Pinar; Ilikci Sagkan Rahsan; Astarci Erhan; Tok Duran; Ozenc Salim; Ural Ali Ugur; Avcu Ferit

来源：Turkish Journal of Medical Sciences, 2015, 45(1): 38-46.

DOI：10.3906/sag-1401-127

• Caffeic acid phenethyl ester
• bortezomib
• multiple myeloma
• in vitro cytotoxicity
• in vivo study

Background/aim: 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.
Materials and 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-kappa B) 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-kappa B 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.
Conclusion: 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.

• 出版日期2015
• 单位中国人民解放军军事医学科学院