Combined antitumor effects of bee venom and cisplatin on
human cervical and laryngeal carcinoma cells and their drug resistant sublines
J Appl Toxicol. 2014 Dec;34(12):1332-41
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
μg ml(–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 μg ml(–1) for HeLa vs.47.64
μg ml(–1) for HeLa CK cells), whereas opposite results were obtained for
cisplatin-resistant laryngeal carcinoma cells (IC(50) values were 51.98 μg
ml(–1) for HEp-2 vs. > 60.00 μg ml(–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.
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