Author/Authors :
ALTAYLI, Ertan Gülhane Military Medical Academy - Department of Medical Biology, Turkey , KORU, Özgür Gülhane Military Medical Academy - Department of Microbiology, Division of Medical Parasitology, Turkey , ÖNGÖRÜ, Önder Gülhane Military Medical Academy - Department of Pathology, Turkey , İDE, Tayfun Gülhane Military Medical Academy - Research and Development Center - Division of Experimental Surgery, Turkey , AÇIKEL, Cengizhan Gülhane Military Medical Academy - Department of Biostatistics, Turkey , SARPER, Meral Gülhane Military Medical Academy - Research and Development Center - Division of Cancer, Stem Cell, and Medical Research, Turkey , ELÇİ, Mualla Pınar Gülhane Military Medical Academy - Research and Development Center - Division of Cancer, Stem Cell, and Medical Research, Turkey , ILIKÇI SAĞKAN, Rahşan Gülhane Military Medical Academy - Departments of Immunology and Allergic Diseases, Turkey , ASTARCI, Erhan Abant İzzet Baysal University - Department of Plant and Animal Production, Turkey , TOK, Duran Turkish Armed Forces Health Command, Health and Veterinary Services, Turkey , ÖZENÇ, Salim Diyarbakır Military Medical Hospital - Department of Family Medicine, Turkey , URAL, Ali Uğur Bayındır Hospital - Department of Stem Cell Transplantation, Turkey , URAL, Ali Uğur Gülhane Military Medical Academy - Research and Development Center - Division of Cancer, Stem Cell, and Medical Research, Turkey , AVCU, Ferit Gülhane Military Medical Academy - Research and Development Center - Division of Cancer, Stem Cell, and Medical Research, Department of Hematology, Turkey
Abstract :
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-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 DNAbinding 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.
