Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin.
Cisplatin (cDDP) is one of the most widely used anticancer-drugs in both therapy and research. However, cDDP-resistance is the greatest obstacle for the successful treatment of cancer patients. In the present study, the possible joint anticancer effect of bee venom (BV), as a natural toxin, and cDDP towards human glioblastoma A1235 cells was evaluated. Treatment with BV alone in concentrations of 2.5-30 μg/ml displayed dose-dependent cytotoxicity towards A1235 cells, as evaluated with different cytotoxicity assays (MTT, Cristal violet and Trypan blue exclusion assay), with an IC50 value of 22.57 μg/ml based on the MTT results. Furthermore, BV treatment induced necrosis, which was confirmed by typical morphological features and fast staining with ethidium-bromide dye. Pre-treatment with BV induced cell sensitization to cDDP, indicating that BV could improve the killing effect of selected cells when combined with cDDP. The isobologram method used to determine the extent of synergism in combining two agents to examine their possible therapeutic effect showed that combined treatment induced an additive and/or synergistic effect towards selected cells depending on the concentration of both. Hence, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. The obtained results indicate that joint treatment with BV could be useful from the point of minimizing the cDDP concentration during chemotherapy, thus reducing and/or postponing the development of drug resistance. Our data, in accordance with previously reported results, suggests that BV could be used in the development of a new strategy for cancer treatment.
Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
Goran
G
Gajski
Laboratory for Genotoxic Agents, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.
Tamara
T
Čimbora-Zovko
Laboratory for Genotoxic Agents, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.
Sanjica
S
Rak
Laboratory for Genotoxic Agents, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.
Maja
M
Osmak
Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia. vgaraj@imi.hr.
Vera
V
Garaj-Vrhovac
Bee venom; Biotoxins; Cisplatin; Combination therapy; Cytotoxicity; Human glioblastoma cells