Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - WoS: 1Citation - Scopus: 1Tomatidine, a Steroidal Alkaloid, Synergizes With Cisplatin to Inhibit Cell Viability and Induce Cell Death Selectively on FLT3-ITD+ Acute Myeloid Leukemia Cells(Humana Press inc, 2024-07-11) Ayvaz, Havva Berre; Yenigul, Munevver; Akcok, Emel Basak Gencer; Gencer Akçok, Emel BaşakBackgroundAcute Myeloid Leukemia (AML) is a hematological cancer that frequently presents with a range of side effects and drug resistance during anticancer drug treatment. The current study aims to achieve increased efficacy by combining lower doses of cisplatin with increasing concentrations of tomatidine in AML cells to increase efficacy.MethodsAnti-proliferative effects of single and combination of cisplatin and tomatidine were assessed via MTT cell viability assay. The Annexin V/Propidium Iodide Double Staining method was used to measure the apoptotic effects of combined tomatidine and cisplatin treatment. Then, Western Blot analysis was performed to measure Poly (ADP-ribose) polymerase (PARP) and Caspase-3 protein expression levels.ResultsCisplatin treatment with lower concentrations displayed high cytotoxic effects on AML cells, compared with tomatidine. The combination of the Inhibitory Concentration (IC) 20 value of cisplatin and increasing doses of tomatidine exhibited a significant decrease in cell viability relative to single treatments. The combination index analysis revealed a mild synergistic effect of cisplatin IC20 and varying tomatidine doses. The apoptosis induced when cisplatin was combined with 500 mu M tomatidine by almost 20%, while the percentage of apoptosis in combination with 1 mM tomatidine was measured by 50% for both cell lines. The upregulation of proapoptotic cleaved-PARP (3.2 and 1.08-fold for THP-1 and MOLM-13, respectively) and downregulation in Caspase-3 (0.23 and 0.13-fold for THP-1 and MOLM-13, respectively) was detected.ConclusionsTogether, the study indicated that when tomatidine combined with cisplatin on AML cell lines, a combinatorial anti-proliferative and apoptotic effect is observed. The combination of cisplatin with tomatidine may be a promising approach.Article Citation - WoS: 14Citation - Scopus: 14Ethacrynic Acid and Cinnamic Acid Combination Exhibits Selective Anticancer Effects on K562 Chronic Myeloid Leukemia Cells(Springer, 2022-05-18) Yenigul, Munevver; Akcok, Ismail; Gencer Akcok, Emel BasakBackground Despite the recent advances in chemotherapy, the outcomes and the success of these treatments still remain insufficient. Novel combination treatments and treatment strategies need to be developed in order to achieve more effective treatment. This study was designed to investigate the combined effect of ethacrynic acid and cinnamic acid on cancer cell lines. Methods The anti-proliferative effect of ethacrynic acid and cinnamic acid was investigated by MTT cell viability assay in three different cancer cell lines. Combination indexes were calculated using CompuSyn software. Apoptosis was assessed by flow cytometric Annexin V-FITC/PI double-staining. The effect of the inhibitors on cell cycle distribution was measured by propidium iodide staining. Results The combination treatment of ethacrynic acid and cinnamic acid decreased cell proliferation significantly, by 63%, 75% and 70% for K562, HepG2 and TFK-1 cells, respectively. A 5.5-fold increase in the apoptotic cell population was observed after combination treatment of K562 cells. The population of apoptotic cells increased by 9.3 and 0.4% in HepG2 and TFK-1 cells, respectively. Furthermore, cell cycle analysis shows significant cell cycle arrest in S and G2/M phase for K562 cells and non-significant accumulation in G0/G1 phase for TFK-1 and HepG2 cells. Conclusions Although there is a need for further investigation, our results suggest that the inhibitors used in this study cause a decrease in cellular proliferation, induce apoptosis and cause cell cycle arrest.Article Cytotoxic and Cytostatic Effects of Targeting mTOR and Hedgehog Pathways in Acute Myeloid Leukemia(Istanbul Univ, 2022-12-29) Cicek, Enes; Kucuktas, Fulya Mina; Yenigul, Munevver; Akcok, Emel Basak GencerObjectives: Acute myeloid leukemia (AML) is a highly aggressive heterogeneous hematopoietic malignancy characterized by a rapid and abnormal proliferation of immature myeloid leukemia cells in the bone marrow and peripheral blood. Aberrant alterations in signal transduction pathways are strongly associated with the progression of AML. This study aimed to investigate cell viability and the cell cycle in AML cells by targeting the Hedgehog and mTOR signaling pathways with rapamycin and GANT61. Materials and Method: The antiproliferative effect of rapamycin and GANT61 was assessed by the MTT cell viability assay in two AML cell lines: CMK and MOLM-13. The effect of the inhibitors on cell-cycle distribution was determined using propidium iodide staining and measured with flow cytometry. Results: Rapamycin, an mTOR inhibitor, and GANT61, a Gli-1 inhibitor, decreased the cell proliferation of CMK and MOLM-13 cells. The IC20 values, which is the drug concentration that inhibits cell growth by 20%, were combined and administered to the cells. The results show the drugs to have a combinatorial inhibitory effect on CMK cells but not on MOLM-13 cells. In addition, the combination of drugs arrested the cells during the G0/G1 phase. Conclusion: This study suggests a novel combination therapy approach for AML via mTOR and Hedgehog signaling pathway inhibition using rapamycin and GANT61, respectively. It also suggest further studies be performed to reveal the mechanism of action.