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

Gajski, Goran; Čimbora-Zovko, Tamara; Rak, Sanjica; Rožman, Marko; Osmak, Maja; Garaj-Vrhova, Vera (2014) Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines. Journal of Applied Toxicology, 34 (12). pp. 1332-1341. ISSN 0260-437X

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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 (IC50 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 (IC50 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.

Item Type: Article
Additional Information: "This is the peer reviewed version of the following articleGajski, Goran; Čimbora-Zovko, Tamara; Rak, Sanjica; Rožman, Marko; Osmak, Maja; Garaj-Vrhova, Vera (2014) Combined antitumor effects of bee venom and cisplatin on human cervical and laryngeal carcinoma cells and their drug resistant sublines. Journal of Applied Toxicology, 34 (12). pp. 1332-1341, which has been published in final form http://onlinelibrary.wiley.com/doi/10.1002/jat.2959/full . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."
Uncontrolled Keywords: Apoptosis; Bee venom; Cisplatin; Cytotoxicity; Drug resistance; Melittin; Necrosis; Tumour cells
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Physical Chemistry
Projects:
Project titleProject leaderProject codeProject type
Stanični odgovor na citotoksične spojeve i razvoj otpornosti-Maja Osmak098-0982913-2748MZOS
Mutageni i antimutageni u ekogenetičkim istraživanjima-Vera Garaj-Vrhovac022-0222148-2125MZOS
Depositing User: Kristina Ciglar
Date Deposited: 18 Jan 2017 16:11
Last Modified: 26 Jan 2017 14:05
URI: http://fulir.irb.hr/id/eprint/3325
DOI: 10.1002/jat.2959

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