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.
KeywordsBiotoxins Bee venom Cisplatin Combination therapy Cytotoxicity Human glioblastoma cells
This work was supported by the Ministry of Science, Education and Sport of the Republic of Croatia (Grant Nos. 022-0222148-2125 and 098-0982913-2748).
Conflict of interest
The authors declare that they have no conflict of interest.
- Alizadehnohi M, Nabiuni M, Nazari Z, Safaeinejad Z, Irian S (2012) The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp. J Venom Res 3:22–27Google Scholar
- Choi KE, Hwang CJ, Gu SM, Park MH, Kim JH, Park JH, Ahn YJ, Kim JY, Song MJ, Song HS, Han SB, Hong JT (2014) Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. Toxins (Basel) 6:2210–2228. doi: 10.3390/toxins6082210 CrossRefGoogle Scholar
- Gajski G, Čimbora-Zovko T, Osmak M, Garaj-Vrhovac V (2011) Bee venom and melittin are cytotoxic against different types of tumor and non-tumor cell lines in vitro. Cancer Res J 4:159–174Google Scholar
- Ip SW, Liao SS, Lin SY, Lin JP, Yang JS, Lin ML, Chen GW, Lu HF, Lin MW, Han SM, Chung JG (2008a) The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. In Vivo 22:237–245Google Scholar
- Ip SW, Wei HC, Lin JP, Kuo HM, Liu KC, Hsu SC, Yang JS, Mei-Dueyang Chiu TH, Han SM, Chung JG (2008b) Bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells. Anticancer Res 28:833–842Google Scholar
- Jin ZJ (1980) Addition in drug combination. Acta Pharmacol Sin 1:70–76Google Scholar
- Jo M, Park MH, Kollipara PS, An BJ, Song HS, Han SB, Kim JH, Song MJ, Hong JT (2012) Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol Appl Pharmacol 258:72–81. doi: 10.1016/j.taap.2011.10.009 CrossRefGoogle Scholar
- Kouros N (2013) New research finds HIV can be killed with bee venom. Monash Bioeth Rev 31:4Google Scholar
- Putz T, Ramoner R, Gander H, Rahm A, Bartsch G, Thurnher M (2006) Antitumor action and immune activation through cooperation of bee venom secretory phospholipase A2 and phosphatidylinositol-(3,4)-bisphosphate. Cancer Immunol Immunother 55:1374–1383. doi: 10.1007/s00262-006-0143-9 CrossRefGoogle Scholar
- Stathopoulos GP (2013) Cisplatin: process and future. J BUON 18:564–569Google Scholar
- Stewart BW, Kleihues P (2003) World cancer report, 2nd edn. IARC Press, LyonGoogle Scholar
- Stuhlmeier KM (2007) Apis mellifera venom and melittin block neither NF-kappa B-p50-DNA interactions nor the activation of NF-kappa B, instead they activate the transcription of proinflammatory genes and the release of reactive oxygen intermediates. J Immunol 179:655–664. doi: 10.4049/jimmunol.179.1.655 CrossRefGoogle Scholar
- Varanda EA, Monti R, Tavares DC (1999) Inhibitory effect of propolis and bee venom on the mutagenicity of some direct- and indirect-acting mutagens. Teratog Carcinog Mutagen 19:403–413. doi: 10.1002/(SICI)1520-6866(1999)19:6<403:AID-TCM4>3.0.CO;2-2 CrossRefGoogle Scholar