Biyomühendislik / Bioengineering

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/208

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Browsing Biyomühendislik / Bioengineering by Subject "Acute myeloid leukemia"

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    Inhibition of PI3K-AKT-mTOR pathway and modulation of histone deacetylase enzymes reduce the growth of acute myeloid leukemia cells
    (HUMANA PRESS INC, 2023) Şansaçar, Merve; Sağır, Helin; Gencer Akçok, Emel Başak; 0000-0002-6559-9144; 0000-0002-1731-5215; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Şansaçar, Merve; Sağır, Helin; Gencer Akçok, Emel Başak
    One of the most widespread forms of blood cancer is known as acute myeloid leukemia (AML) which has an incidence of 80% with poor prognosis. Although there are different treatment methods for AML in clinic, the heterogeneity and complexity of the disease show that new treatments are needed. The aim of this study is to investigate the anticancer effects of inhibition of PI3K and HDAC enzymes on CMK and MOLM-13 AML cells lines. We demonstrated that the combination of LY294002 with SAHA and Tubastatin A significantly decreased the cell viability of both cell lines. In contrast, the LY294002 and PCI-34051 combination did not show a significant difference compared to the single LY294002 administration. The combination treatment of LY294002 and HDAC inhibitors did not induce apoptosis significantly. However, LY294002 + SAHA and LY294002 + PCI-34051 resulted in G0/G1 and G2/M cell cycle arrest in CMK cells, respectively. On the other hand, compared to control cells, LY294002 + SAHA and LY294002 + PCI-34051 led to G0/G1 phase arrest in MOLM-13. Furthermore, the LY294002 + PCI-34051 combination elevated the expression rate of LC3BII/I, an autophagy marker, in CMK cells by 2.5-fold. Our study revealed that the combinations of PI3K inhibitor and HDAC inhibitors showed a synergistic effect and caused a reduction in cell viability and increased cell cycle arrest on MOLM-13 and CMK cell lines. In addition, the expression of LC3BII was elevated in the CMK cell line. In conclusion, although more mechanistic studies are required, a combinational inhibition of PI3K and HDAC could be a promising approach for AML.
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    Rapamycin and Niacin combination induces apoptosis and cell cycle arrest through autophagy activation on acute myeloid leukemia cells
    (SPRINGER NATURE LINK, 2025) Subay, Lale Beril; Akcok, Emel Basak Gencer; Akcok, Ismail; 0000-0002-5444-3929; 0000-0002-6559-9144; 0009-0003-3594-4781; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Subay, Lale Beril; Akcok, Emel Basak Gencer; Akcok, Ismail
    BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by disorders in stem cell differentiation and excessive proliferation resulting in clonal expansion of dysfunctional cells called myeloid blasts. The combination of chemotherapeutic agents with natural product-based molecules is promising in the treatment of AML. In this study, we aim to investigate the anti-cancer effect of Rapamycin and Niacin combination on THP-1 and NB4 AML cell lines.Methods and ResultsThe anti-proliferative effects of Rapamycin and Niacin were determined by MTT cell viability assay in a dose- and time-dependent manner. The combination indexes were calculated by isobologram analysis. Furthermore, apoptosis was investigated by Annexin-V/Propidium Iodide(PI) double staining and cell cycle distribution was measured by PI staining. The expression levels of autophagy-related proteins were detected by western blotting. The combination of Rapamycin and Niacin synergistically decreased cell viability of AML cell lines. The combination treatment induced the apoptotic cell population of THP-1 and NB4 by 4.9-fold and 7.3-fold, respectively. In THP-1 cells, the cell cycle was arrested at the G2/M phase by 10% whereas the NB4 cells were accumulated at the G0/G1 phase. The combination treatment decreased Akt and p-Akt expression. Besides, the ATG7 expression was reduced by combination treatment on THP-1 cells. Similarly, the ATG5 level was downregulated in NB4 cells. The level of LC3B-II/LC3B-I, which is an indicator of autophagy flux, was upregulated in THP-1 and NB4 cells.ConclusionAlthough further studies are required, the combination of Rapamycin and Niacin combats cell proliferation by inducing cellular apoptosis, cell cycle arrest and autophagy activation.