Ellagic Acid and Resveratrol Prevent the Development of Cisplatin Resistance in the Epithelial Ovarian Cancer Cell Line A2780
| Autor: | Laura H. Engelke, Peter Proksch, Alexandra Hamacher, Matthias U. Kassack |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Antioxidant endocrine system diseases medicine.medical_treatment cisplatin resveratrol Pharmacology Resveratrol 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine ellagic acid medicine Cytotoxicity Cisplatin business.industry A2780 medicine.disease ovarian cancer 030104 developmental biology Oncology chemistry Cell culture Apoptosis 030220 oncology & carcinogenesis Ovarian cancer business resistance development Research Paper Ellagic acid medicine.drug |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| DOI: | 10.7150/jca.13754 |
| Popis: | Purpose. Several studies have shown that natural compounds like resveratrol or ellagic acid have anticancer and antioxidant properties and can stimulate apoptosis in many cancer cell lines. The aim of this study was to elucidate if resveratrol or ellagic acid, respectively, could improve the efficacy of cisplatin in ovarian cancer. Methods. As a cellular resistance model, the epithelial ovarian cancer cell line A2780 and its cisplatin-resistant subclone A2780CisR were used. A2780CisR was obtained by intermittent treatment of A2780 with cisplatin for 26 weekly cycles and showed a 4-6-fold increased resistance towards cisplatin compared to A2780. Results. Pretreatment with resveratrol or ellagic acid 48 h prior to treatment with cisplatin showed a moderate enhancement of cisplatin cytotoxicity in A2780CisR cells (shift factors were 1.6 for ellagic acid and 2.5 for resveratrol). However, intermittent treatment of A2780 with cisplatin for 26 weekly cycles in permanent presence of resveratrol or ellagic acid, respectively, completely prevented the development of cisplatin resistance. The generated cell lines named A2780Resv and A2780Ellag displayed functional characteristics (migration, proliferation, apoptosis, activation of ErbB3, ROS generation) similar to the parental cell line A2780. Conclusion. In conclusion, weekly intermittent treatment cycles of cisplatin-sensitive ovarian cancer cells with cisplatin retain cisplatin chemosensitivity in permanent presence of ellagic acid or resveratrol, respectively, whereas clinically relevant cisplatin chemoresistance develops in the absence of ellagic acid or resveratrol. Use of natural phenolic compounds may thus be a promising approach to prevent cisplatin resistance in ovarian cancer. |
| Databáze: | OpenAIRE |
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