Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Račkauskas, R; Zhou, D; Ūselis, S; Strupas, K; Herr, I; Schemmer, P.
Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the downregulation of anti-apoptotic proteins.
Oncol Rep. 2017; 37(6):3660-3666
Doi: 10.3892/or.2017.5622
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- Führende Autor*innen der Med Uni Graz
- Schemmer Peter
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- Abstract:
- Cholangiocarcinoma (CCC) is an aggressive malignancy with poor therapeutic options and pronounced chemotherapy resistance. The bioactive broccoli substance, sulforaphane (SFN), is a promising new therapeutic option since it has been found to induce therapeutic effects in both experimental and epidemiological studies in various tumor entities. Thus, the present study was designed to assess the effect of SFN on cisplatin sensitivity in CCC. Human HuCCT-1 and TFK-1 cells, representing intrahepatic and extrahepatic CCC, respectively, were treated with cisplatin and SFN. Viability, the platinated DNA content, and apoptosis were assessed using both MTT assay and flow cytometry, while western blotting was used to analyze the expression of proteins involved in apoptosis and DNA damage. Whereas cisplatin was largely ineffective, SFN only therapy significantly decreased the viability of both CCC cell lines. The combination of SFN with cisplatin increased cisplatin cytotoxicity, which was particularly pronounced relatively early at 36 h after treatment. Apoptosis, which was reflected by the cleavage of caspase-3 and PARP, was significantly enhanced. Notably, only cisplatin was found to induce the expression of proteins involved in the DNA damage response; however, the presence of SFN appeared to enable otherwise cisplatin-resistant cells to undergo apoptosis. Due to the fact that SFN did not enhance the DNA platination levels upon cisplatin treatment, SFN may have exerted its activity via the inhibition of the anti-apoptotic proteins Bcl-2 and XIAP, as we observed. Data presented in the present study clearly demonstrated that SFN significantly decreased the drug resistance to cisplatin in human CCC. This highlights dietary co-treatment as a viable new treatment option for CCC.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Combined Chemotherapy Protocols - administration & dosage
- Apoptosis - drug effects
- Caspase 3 - genetics
- Cell Line, Tumor -
- Cell Proliferation - drug effects
- Cholangiocarcinoma - diet therapy
- Cholangiocarcinoma - drug therapy
- Cholangiocarcinoma - genetics
- Cholangiocarcinoma - pathology
- Cisplatin - administration & dosage
- Cisplatin - adverse effects
- Drug Resistance, Neoplasm - genetics
- Gene Expression Regulation, Neoplastic - drug effects
- Humans -
- Isothiocyanates - administration & dosage
- Proto-Oncogene Proteins c-bcl-2 - genetics
- Find related publications in this database (Keywords)
- cholangiocarcinoma
- cisplatin
- DNA damage
- drug resistance
- sulforaphane