Akademik Veri Yönetim Sistemi
12th International Drug chemistry Congress, Antalya, Türkiye, 7 - 10 Mart 2024, ss.127
Acute 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 blasts1. AML has a dysregulated PI3K/AKT/mTOR signaling pathway which regulates autophagy2,3. Autophagy is commonly defined as a cellular process that ensures the survival of cells by regulating and maintaining a delicate equilibrium between the degradation, synthesis, and reutilization of cellular components4. Rapamycin, an immunosuppressant and antiproliferative agent, potently inhibits mTOR activity5. Therefore, mTOR inhibition results in autophagy activation. Niacin, which is also known as vitamin B3 or nicotinic acid, is a potent anticancer agent that regulates autophagy via the GPR109A/AMPK/NRF-2 signaling pathway6. The combination therapy is a promising treatment strategy to combat cancer by increasing the treatment efficacy and reducing the side effects of chemotherapy7. In this study, we aim to investigate the anti-cancer effect of the combination of Rapamycin and Niacin on AML cell lines; THP-1 and NB4. The MTT cell viability results showed that both Rapamycin and Niacin significantly reduce the proliferation of THP-1 and NB4 cells at 48 hours compared to untreated controls in a time- and dose-dependent manner. In addition, the combination of Rapamycin and Niacin synergistically reduce the cell proliferation on THP-1 and NB4 cell lines compared to control and single-treated cells. In the apoptosis assay, simultaneous exposure of THP-1 cells to Rapamycin and Niacin increased the early and late apoptotic cell population by 4.5-fold. Moreover, for NB4 cells, the results revealed that there was a 7-fold increase in apoptotic cell population relative to the control. Cell cycle analysis of THP-1 cells demonstrated that when 5μM Rapa+ 20 mM Niacin was administered, the G2/M phase arrest was increased by 10%. However, the NB4 cells were arrested in G0/G1 phase in response to 10μM Rapa + 5 mM Niacin combination. Overall, the Rapamycin and Niacin combination treatment reduced cell proliferation by inducing apoptosis and arresting cell cycle on AML cells.