Cucurbitacin B Restored Cisplatin Sensitivity of Ovarian Cancer Cells by Altering Fatty Acid Synthase and LRP-130 Protein Expression
Fardous El-Senduny, F.1,3, Farid Badria, A.2, Ahmed EL-Waseef, M.3, Eduardo Callegari, A.4 & Fathi Halaweish1*
1Chemistry and Biochemistry Department, South Dakota State University, Brookings, USA
2Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Egypt
3Chemistry Department, Faculty of Science, Mansoura University, Egypt
4Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, USA
Dr. Fathi Halaweish, Chemistry and Biochemistry Department, South Dakota State University, Brookings, USA.
Keywords: Ovarian Cancer; Cisplatin Resistance; Cucurbitacin B; Fatty Acid Synthesis; Protein Metabolism
The first line in chemotherapy for ovarian cancer is platinum-based drugs. Despite combination treatment regimes, the 5-year survival rate still in decrease due to the resistance of the recurrent disease to the treatment. Finding a natural product that can restore cell’ sensitivity to the common therapeutic drugs is needed. Recent finding in our research showed that cucurbitacin B sensitizes the cisplatin-resistant ovarian cancer cell lines to the cytotoxicity of cisplatin. The aim of this work is to investigate the mechanism behind the sensitization by cucurbitacin B and analyzing change in protein expression after treatment with either cucurbitacin B, cisplatin or combination of both compounds. The protein lysate was subjected to 2D-nano-UPLC-MS/MS analysis. Data analysis showed that cucurbitacin B as a single compound or in combination with cisplatin treatment mainly altered proteins involved in fatty acid synthesis, antioxidant system, protein folding, cytoskeleton, DNA replication, translation and chromatin assembly. Western blot validation for FASN, LPPRC and H2A.x was in agreement with the proteomic data confirming the possible mechanism of sensitization effect of cucurbitacin B via the change in proteins involved in the induction of apoptosis and inhibition of survival pathways.
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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