Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines

Abstract

In the present study, we investigated the possible combined anticancer ability of bee venom (BV) and cisplatin towards two pairs of tumour cell lines: parental cervical carcinoma HeLa cells and their cisplatin-resistant HeLa CK subline, as well as laryngeal carcinoma HEp-2 cells and their cisplatin-resistant CK2 subline. Additionally, we identified several peptides of BV in the BV sample used in the course of the study and determined the exact concentration of MEL. BV applied alone in concentrations of 30 to 60 μgml -1 displayed dose-dependent cytotoxicity against all cell lines tested. Cisplatin-resistant cervical carcinoma cells were more sensitive to BV than their parental cell lines (IC 50 values were 52.50 μgml -1 for HeLa vs. 47.64 μgml -1 for HeLa CK cells), whereas opposite results were obtained for cisplatin-resistant laryngeal carcinoma cells (IC 50 values were 51.98 μgml -1 for HEp-2 vs. > 60.00 μgml -1 for CK2 cells). Treatment with BV alone induced a necrotic type of cell death, as shown by characteristic morphological features, fast staining with ethidium-bromide and a lack of cleavage of apoptotic marker poly (ADP-ribose) polymerase (PARP) on Western blot. Combined treatment of BV and cisplatin induced an additive and/or weak synergistic effect towards tested cell lines, suggesting that BV could enhance the killing effect of selected cells when combined with cisplatin. Therefore, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. Our results suggest that combined treatment with BV could be useful from the point of minimizing the cisplatin concentration during chemotherapy, consequently reducing and/or postponing the development of cisplatin resistance.

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

“…These components have known cytotoxic effects towards different cells (Son et al 2007;Oršolić 2012;Gajski and Garaj-Vrhovac 2013) and are likely to be responsible for the effects observed in our study as well. In our previous study, peptides MEL, apamin, MCD peptide and tertiapin were identified as components of BV and we determined the concentration of MEL and its mass fraction in a BV sample, estimating it at 0.19 (Gajski et al 2014). The identified peptides are also in agreement with earlier findings concerning peptide components of BV (Son et al 2007;Oršolić 2012).…”

“…Until now, it has been demonstrated that BV has the ability to inhibit the growth of several types of cancer cell lines and induce cytotoxic, immunomodulatory, apoptotic and necrotic effects both in vivo and in vitro (Son et al 2007;Oršolić 2012;Gajski et al 2014;Liu et al 2014). Previously, we reported that BV is cytotoxic towards different types of tumour and non- tumour cells in vitro ) with preferential cytotoxicity against tumour cells.…”

“…In our previous study (Gajski et al 2014), we investigated the combined anticancer ability of BV and cDDP towards two pairs of tumour cell lines: parental cervical carcinoma HeLa and laryngeal carcinoma HEp-2 cells, and their cDDP-resistant HeLa CK and CK2 sublines, respectively. The results showed that BV applied alone displayed dose-dependent cytotoxicity against all cell lines tested triggering a necrotic type of cell death.…”

“…In order to overcome cDDP resistance and reduce normal cell toxicity, combination therapies of cDDP with other drugs, especially natural toxins have been highly considered. In the search for new cancer agents, biotoxins have recently attracted attention owing to their novel mode of actions and decreased possibility of resistance development (Gaspar et al 2013;Gajski et al 2014;Liu et al 2014). Bee venom (BV) has been used in oriental medicine as a source of drugs to cure different disorders (Son et al 2007;Oršolić 2012;Liu et al 2014;Premratanachai and Chanchao 2014).…”

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.…”