Antitumour action on human glioblastoma A1235 cells through cooperation of bee venom and cisplatin

Abstract

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.

Identification and quantification of honeybee venom constituents by multiplatform metabolomics

“…Many in vitro and in vivo studies indicated that HBV has a direct antitumor effect and leads to inhibition of proliferation, metastasis, angiogenesis, and induction of apoptosis 1 , 25 . Moreover, some promising findings suggested that HBV can be used in combination with standard chemotherapy, e.g., cisplatin 26 , 27 . Another important application of HBV is venom immunotherapy, which is an effective treatment of severe honeybee sting-induced allergic reactions 28 .…”

Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells

“…Bee venom makes sense as a complement to cisplatin: it has protective effects in many areas of the body such as the blood and nerves [ 6 ]; it is able to inhibit cell growth in tumours [ 7 ]; and has even been examined and used in complementary treatments that are necessitated by the effects of chemotherapy, such as allodynia [ 8 ] and neuropathy [ 9 ]. Cisplatin in combination with bee venom has been successfully used against human cervical and laryngeal carcinoma cells, including their drug-resistant sublines [ 10 ], and human glioblastoma [ 11 ]. Several studies have found that phospholipase A 2 , another component of bee venom, not only mitigates the negative impact of cisplatin on kidneys [ 12 ], but also boosts regulatory T cell (Treg) numbers in the spleen and enhances Treg traffic to the kidneys following cisplatin exposure.…”

An overview of the bioactive compounds, therapeutic properties and toxic effects of apitoxin

“…In spite of the promising properties that are attracting much interest from pharmacological and biotechnological fields, MLT (whose initial structure is helical, when embedded in a lipid bilayer) can change to a dimeric form that destabilizes and alters artificial lipid bilayers containing dioleoylphosphatidylcholine (Somwongin et al, 2018). Therefore, MLT may induce morphologic changes in a dose-dependent manner, being a nonselective cytolytic peptide that may induce the lysis of red blood cells and human peripheral blood lymphocytes, among others (Gajski et al, 2016). Indeed, while in small doses MLT has antiinflammatory effects, increases capillary permeability, in higher doses it may cause inflammation, itching, irritation and local pain (Lee and Bae, 2016).…”

“…Phospholipase A 2 has been reported to be the most abundant enzyme of BV, corresponding to 10-12% of its dry weight matter (dos Santos-Pinto et al, 2018). Due to its high molecular weight and strong antigenicity, this enzyme has been pointed as the major cause of the systemic allergic reactions to BV (Gajski et al, 2016;Hossen et al, 2016). On the other hand, several recent reports unveiled the potentiality of PLA 2 in the treatment of human disorders (Table 1) including Parkinson's disease, asthma, several types of cancer, as well as immune mediated disorders like cisplatin-induced nephrotoxicity, hepatotoxicity and Lupus nephritis (Ratcliffe et al, 2014).…”