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    Effect of napabucasin and doxorubicin via the Jak2/Stat3 signaling pathway in suppressing the proliferation of neuroblastoma cells
    (Acta Cirurgica Brasileira, 2024) Unlu, Ilker; Tuncer, Mehmet Cudi; Ozdemir, Ilhan
    Purpose: Napabucasin (NP) is a natural compound that can suppress cancer cell proliferation and cell cycle by inhibition of the signal transducer and activator of transcription 3 (STAT3) gene. We examined the effects of NP on the proliferation and invasion of neuroblastoma cells (SH-SY5Y). Methods: Human neuroblastoma SH-SY5Y cell line was used in this study. NP was administered to groups at the doses of 0.3-1 mu M. Cell viability was analyzed by MTT assay. Real-time quantitative reverse transcription polymerase chain reaction and western blot analysis assessed the expressions of interleukin (IL)-6 dependent Jak2/Stat3 signaling pathway. The MTT cell viability method was applied to determine the antagonistic-synergistic effects and inhibitory concentration (IC50) doses of doxorubicin (DX) and NP. Results: It was determined that 0.3-1 mu M doses of NP killed the cells almost completely after 48 hours, and also that Jak2/Stat3 expressions decreased dose-dependently via IL-6. At the protein level, NP and DX were found to reduce Jak2 and Stat3 levels. Conclusion: NP showed that it suppresses the proliferation of neuroblastoma cells. Due to its inhibitory effect on Jak2 and Stat3, it can be used to prevent invasion of SH-SY5Y cells. NP, which can inactivate Jak2/Stat3, can be used as a treatment agent by combining with DX in proliferation pathway in neuroblastoma.
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    Effects of Curcumin and Doxorubicin on the Viability of Neuroblastoma Cancer Cell Line
    (2024) Ünlü, İlker; Ozdemır, Ilhan; Öztürk, Şamil; Tuncer, Mehmet Cudi
    Aim: Neuroblastoma has a very important place among childhood diseases, and despite all the methods used in treatment, it is very difficult to prevent neuroblastoma invasion. The number of studies showing that curcumin, the most active component of turmeric, is not toxic, is increasing day by day. In this study, the anticancer activities of curcumin (Cur), one of the important active compounds, were demonstrated in the Neuroblastoma cancer cell line (Na2B). Method: Neuroblastoma cell line was used in the study. To determine the IC50 doses of Dox and Cur, Na2B cells line were cultivated with an automatic pipette. MTT analysis was performed to analyze cell survival (viability). Inhibition levels in the cells were determined at 24 and 48 hours. Results: While the IC50 of Na2B cell proliferation was approximately 124.5 uM at the 48th hour in Dox-treated cells, the IC50 value of Cur at the 48th hour was found to be 224.6 uM. Conclusion: These results showed that Cur could be an alternative agent in the treatment of neuroblastoma, and its fewer side effects compared to other chemotherapeutic agents such as Dox would increase its preferability.
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    Histopathological Changes in The Spinal Cord Tissue of Rats Administered an Experimental Mussel Diet
    (2024) Ünlü, İlker; Özdemir, Ilhan; Tuncer, Mehmet Cudi; Öztürk, Şamil
    Aim: Regional eating habits show that it causes neurodegenerative problems due to heavy metals that can accumulate in consumed foods and affect tissues such as the nervous system. Since crustaceans such as mussels feed by filtering the water, they are exposed to toxic plankton and various chemicals, especially heavy metals. Due to the limitations of experimental studies on this subject, the effects of mussel consumption on the spinal cord were investigated. Methods: In this study, histopathological changes in the spinal cord tissue of rats fed with shellfish collected from the Dardanelles were determined. The subjects were divided into two groups, and the first group was fed standard rat food for 4 weeks, and the second group was fed a mussel diet. At the end of the study, spinal cord tissue samples taken from rats were subjected to routine histopathological procedures and evaluated under a light microscope. Results: In the experimental group, a decrease in the number of neurons in the medulla spinalis and an increase in the number of astrocytes were noted. TUNEL staining showed that apoptosis occurred intensively in glial cells, but did not occur in anterior and posterior horn motor neurons. Conclusion: The findings showed that long-term mussel consumption can cause axonal damage in motor and sensory neurons and degeneration in glial cells. For this reason, it is important for health that marine diets in coastal areas are made with healthy and hygienic products.
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    Napabucasin Inhibits Proliferation and Migration of Glioblastoma Cells (U87) by Regulating JAK2/STAT3 Signaling Pathway
    (MDPI, 2024) Unlu, Ilker; Ozdemir, Ilhan; Tuncer, Mehmet Cudi
    Background and Objectives: Napabucasin (NP) was discovered as a natural compound that suppresses cancer stemness by inhibiting the signal transducer and activator of the transcription 3 (STAT3) signaling pathway. In this study, the anti-proliferative and apoptotic effects of NP and the chemotherapy agent doxorubicin (DX), a natural compound, on glioblastoma cells (U87) were investigated. Materials and Methods: In this study, the effects of NP and DX on cell viability on the glioblastoma U87 cell line were determined by MTT test. Expressions of Jak2/Stat3 genes were examined by qRT-PCR. Apoptosis was evaluated by Hoescht 33258 staining. Moreover, NP, its antagonistic-synergistic effects and IC50 doses of the combined treatment of DX were determined. Results: Napabucacin and doxorubicin were found to inhibit glioblastoma U87 cell proliferation. It was determined that NP applied in the range of 0.3-1 mu M and its combination with DX killed almost all of the glioblastoma cells in 48 h of application. Additionally, it was observed that Jak2/Stat3 expressions downregulated. Conclusions: These results show that NP suppresses the proliferation of glioblastoma cells. It was shown that the combination of NP and DX can prevent invasion of the U87 cell line due to its Jak2/Stat3 inhibitory effect. Since it can suppress Jak2/Stat3, an important cancer cell proliferation pathway in glioblastoma, the combination of NP and DX can be used as an alternative treatment agent. But no synergistic effect of NP and DX on the U87 cells of the glioblastoma cell line was observed.