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

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-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.

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.

• Authors: Ertan Altayli, Özgür Koru, Önder Öngörü, Tayfun İde, Cengizhan Açikel, Meral Sarper, Mualla Pınar Elçi, Rahşan Ilikçi Sağkan, Erhan Astarci, Duran Tok, Salim Özenç, Ali Uğur Ural, Ferit Avcu
• Journal: Turkish journal of medical sciences (Turk J Med Sci) Vol. 45 Issue 1 Pg. 38-46 ( 2015) ISSN: 1300-0144 [Print] Turkey
• PMID: 25790528 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Boronic Acids
• Caffeic Acids
• Interleukin-6
• NF-kappa B
• Pyrazines
• Bortezomib
• caffeic acid phenethyl ester
• Phenylethyl Alcohol

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Boronic Acids (pharmacology)
• Bortezomib
• Caffeic Acids (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Female
• Humans
• Interleukin-6 (metabolism)
• Mice
• Mice, Inbred BALB C
• Multiple Myeloma
• NF-kappa B (metabolism)
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Pyrazines (pharmacology)
• Survival Analysis