Moleküler Biyoloji ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/209

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Browsing Moleküler Biyoloji ve Genetik Bölümü Koleksiyonu 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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    Tomatidine, a Steroidal Alkaloid, Synergizes with Cisplatin to Inhibit Cell Viability and Induce Cell Death Selectively on FLT3-ITD+ Acute Myeloid Leukemia Cells
    (SPRINGER NATURE Link, 2024) Ayvaz, Havva Berre; Yenigül, Münevver; Gencer Akçok, Emel Başak; 0000-0002-5873-7879; 0000-0003-0468-721X; 0000-0002-6559-9144; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Ayvaz, Havva Berre; Yenigül, Münevver; Gencer Akçok, Emel Başak
    Background: Acute 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. Methods: Anti-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. Results: Cisplatin 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 µM 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. Conclusions: Together, 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.