title: 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 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.
authors.forename: Goran
authors.initials: G
authors.lastname: Gajski
authors.forename: Tamara
authors.initials: T
authors.lastname: Čimbora-Zovko
authors.forename: Sanjica
authors.initials: S
authors.lastname: Rak
authors.forename: Marko
authors.initials: M
authors.lastname: Rožman
authors.forename: Maja
authors.initials: M
authors.lastname: Osmak
authors.forename: Vera
authors.initials: V
authors.lastname: Garaj-Vrhovac
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D001514:Bee Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology
chemical_list: D001514:Bee Venoms; D002945:Cisplatin