Anti-Cancer Effect of Fluorinated Caffeic Acid Phenethyl Ester (FCAPE) on Human Multiple Myeloma Cells

Introduction: Multiple myeloma (MM) is a plasma cell malignancy in the bone marrow. Our previous study found that caffeic acid phenethyl ester (CAPE) can inhibit MM cell growth. The objective of this study is to determine if fluorinated caffeic acid phenethyl ester (FCAPE), a novel derivative of CAPE, induces apoptosis in MM cells and to elucidate the role of oxidative stress in its mechanism of action. METHODS: Cultured MM cell lines RPMI 8226 and NCI-H929 and its normal cell counterpart, human peripheral blood B cells (HPBB), were exposed to FCAPE (0 ~ 50 μM) for 24, 48, or 72 hours. Cell viability was measured using the Presto Blue assay. Apoptosis of RPMI 8226 cells after 24 hour incubation with FCAPE were measured using a flow cytometer. Western blot analysis was done to determine the role of pro and anti-apoptotic proteins from RPMI 8226 cells treated with FCAPE for 24 hours. RPMI 8226 cells were incubated for an hour with N-acetyl cysteine (NAC, 0 ~ 1 mM), a known antioxidant, followed by incubation with 30 μM FCAPE for 24 and 48 hours, respectively. RESULTS: FCAPE decreased viability of both MM cells without affect growth of HPBB cells. Numbers of apoptotic cells were increased corresponding to the increase of FCAPE concentrations. Expressions of caspase-3 and PARP, a target protein of caspase 3, were significantly altered in a pattern indicating FCAPE induction of apoptosis. Anti-apoptotic proteins, MCL-1 and BCL-XL, were significantly decreased. Pre-treatment of NAC decreased the cytotoxic effect of FCAPE on RPMI 8226 cells. CONCLUSIONS: FCAPE demonstrated cytotoxic effects in MM cells in a dose and time-dependent manner. Apoptosis of RPMI 8226 cells were induced by FCAPE in a dose-dependent manner within 24 hours. Pretreatment of antioxidant NAC intervene the inhibitory effect of FCAPE on RPMI 8226 cell growth. The results provide insight into the potential mechanism of FCAPE inhibition of multiple myeloma cell growth