Cucurbitacin E shows synergistic effect with sorafenib by inducing apoptosis in hepatocellular carcinoma cells and regulates Jak/Stat3, ERK/MAPK, PI3K/Akt/mTOR signaling pathways

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dc.authoridTürköz, Yusuf/0000-0001-5401-0720
dc.authoridUremis, Muhammed Mehdi/0000-0003-2296-2422
dc.authorwosidTürköz, Yusuf/ABG-7931-2020
dc.authorwosidUremis, Muhammed Mehdi/HKP-0531-2023
dc.contributor.authorUremis, Muhammed Mehdi
dc.contributor.authorUremis, Nuray
dc.contributor.authorTurkoz, Yusuf
dc.date.accessioned2024-08-04T20:54:29Z
dc.date.available2024-08-04T20:54:29Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractObjective: Cucurbitacin E (CuE), a natural compound found in medicinal plants such as Ecballium Elaterium, has demonstrated antiproliferative and apoptotic effects in various cancer cell types due to its tetracyclic triterpenoid structure. Sorafenib, a multi-tyrosine kinase inhibitor, is commonly used in hepatocellular carcinoma (HCC) treatment. This study aimed to investigate the anticancer effect of CuE alone and in combination with sorafenib on HepG2 cells.Methods: CuE was extracted from Ecballium Elaterium fruit juice and quantitatively evaluated using HPLC. The effect of sorafenib and CuE on cell growth inhibition was determined using the MTT test. Cell cycle progression and apoptosis were assessed using flow cytometry. Mitochondrial damage was evaluated with & UDelta;& psi;m, and DNA damage was assessed using the comet assay. The expression of Jak2/Stat3, PI3K/Akt/mTOR, MAPK, and Bcl-2 family-related genes and proteins were analyzed using western blot and qRT-PCR, respectively.Results: Both CuE (0.1-5 & mu;M) and sorafenib (0.5-10 & mu;M) exhibited dose-and time-dependent antiproliferative and cytotoxic effects against the HepG2 cell line. Both compounds induced apoptosis in HepG2 cells and halted the cell cycle in the G2/M phase while causing mitochondrial and DNA damage. Both compounds down regulated Jak2/Stat3, PI3K/Akt/mTOR, MAPK signaling pathway proteins, and Bcl-xL levels, while up regulated Caspase-9 and Bax protein levels.Conclusion: Based on the results of this study, it can be concluded that CuE alone or in combination with sorafenib has the potential to be an effective therapeutic option for the treatment of HCC by inducing apoptosis and regulating multiple signaling pathways.en_US
dc.description.sponsorshipBayer Health Care Pharmaceuticals Incen_US
dc.description.sponsorshipFor providing the Sorafenib pure substance for this research study, the authors are thankful to Bayer Health Care Pharmaceuticals Inc.en_US
dc.identifier.doi10.1016/j.steroids.2023.109261
dc.identifier.issn0039-128X
dc.identifier.issn1878-5867
dc.identifier.pmid37355001en_US
dc.identifier.scopus2-s2.0-85163858228en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.steroids.2023.109261
dc.identifier.urihttps://hdl.handle.net/11616/101442
dc.identifier.volume198en_US
dc.identifier.wosWOS:001035566800001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Science Incen_US
dc.relation.ispartofSteroidsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCucurbitacin Een_US
dc.subjectSorafeniben_US
dc.subjectHCCen_US
dc.subjectAnti-canceren_US
dc.subjectSynergestic effecten_US
dc.titleCucurbitacin E shows synergistic effect with sorafenib by inducing apoptosis in hepatocellular carcinoma cells and regulates Jak/Stat3, ERK/MAPK, PI3K/Akt/mTOR signaling pathwaysen_US
dc.typeArticleen_US

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