Propolis changes the anticancer activity of temozolomide in U87MG human glioblastoma cell line

Background: Propolis is a honey bee product which contains many active compounds, such as CAPE or chrysin, and has many beneficial activities. Recently, its anti-tumor properties have been discussed. We have tested whether the ethanolic extract of propolis (EEP) interferes with temozolomide (TMZ) to inhibit U87MG cell line growth. Methods: The U87MG glioblastoma cell line was exposed to TMZ (10-100 mu M), EEP (10-100 mu g/ml) or a mixture of TMZ and EEP during 24, 48 or 72 hours. The cell division was examined by the H-3-thymidine incorporation, while the western blot method was used for detection of p65 subunit of NF-kappa B and ELISA test to measure the concentration of its p50 subunit in the nucleus. Results: We have found that both, TMZ and EEP administrated alone, had a dose-and time-dependent inhibitory effect on the U87MG cell line growth, which was manifested by gradual reduction of cell viability and alterations in proliferation rate. The anti-tumor effect of TMZ (20 mu M) was enhanced by EEP, which was especially well observed after a short time of exposition, where simultaneous usage of TMZ and EEP resulted in a higher degree of growth inhibition than each biological factor used separately. In addition, cells treated with TMZ presented no changes in NF-kappa B activity in prolonged time of treatment and EEP only slightly reduced the nuclear translocation of this transcription factor. In turn, the combined incubation with TMZ and EEP led to an approximately double reduction of NF-kappa B nuclear localization. Conclusions: We conclude that EEP presents cytotoxic properties and may cooperate with TMZ synergistically enhancing its growth inhibiting activity against glioblastoma U87MG cell line. This phenomenon may be at least partially mediated by a reduced activity of NF-kappa B.