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

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.