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DOI :10.26650/IstanbulJPharm.2024.1336667   IUP :10.26650/IstanbulJPharm.2024.1336667    Tam Metin (PDF)

The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer

Elif Kaya TilkiSelin Engür Öztürk

Background and Aims:Poorprognosisinlungcancerisassociatedwithtumor-associatedmacrophages(TAMs)thatexhibitM2c like behaviours that support multiple pathways in the tumour microenvironment. The interplay between epigenetic modifications and the ubiquitin-proteasome pathway involves three key mechanisms: regulation of epigenetic enzymes by ubiquitin, interaction between ubiquitin and epigenetic modifiers, and epigenetic silencing of critical genes involved in cellular processes. Therefore, we investigated the effects of ixazomib, a proteasome inhibitor, on gene expression changes in epigenetic chromatin modification enzymes in a co-culture of M2c macrophages and A549 lung cancer cells.

Methods: The IC50 concentration of ixazomib was determined to be 2.19 μM using a real-time cell analyser. THP-1 monocytes were polarised into M0 macrophages with 100 ng/mL phorbol 12-myristate 13-acetate (PMA), rested, and then exposed to 1 mM hydrocortisone to becomeM2cmacrophages.A549cellswereseededinthelowerchamberofaco-cultureplate.M2cmacrophages were then co-cultured with A549 cells for 24 h with or without 2.19 μM ixazomib. After being isolated, mRNA was converted to cDNAand analysed using a gene panel with RT-PCR.

Results: The findings showed that 56 genes had exceptionally high expression levels (up to 1848-fold. Ixazomib downregulated these overexpressed genes.

Conclusion: Ixazomib effectively modulates the expression of genes involved in epigenetic chromatin modification in the lung cancer microenvironment, indicating its utility in lung cancer therapy. Further studies are needed to explore the combined use of epigenetic drugs and proteasome inhibitors.


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APA

Kaya Tilki, E., & Engür Öztürk, S. (2024). The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer. İstanbul Journal of Pharmacy, 54(2), 215-222. https://doi.org/10.26650/IstanbulJPharm.2024.1336667


AMA

Kaya Tilki E, Engür Öztürk S. The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer. İstanbul Journal of Pharmacy. 2024;54(2):215-222. https://doi.org/10.26650/IstanbulJPharm.2024.1336667


ABNT

Kaya Tilki, E.; Engür Öztürk, S. The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer. İstanbul Journal of Pharmacy, [Publisher Location], v. 54, n. 2, p. 215-222, 2024.


Chicago: Author-Date Style

Kaya Tilki, Elif, and Selin Engür Öztürk. 2024. “The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer.” İstanbul Journal of Pharmacy 54, no. 2: 215-222. https://doi.org/10.26650/IstanbulJPharm.2024.1336667


Chicago: Humanities Style

Kaya Tilki, Elif, and Selin Engür Öztürk. The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer.” İstanbul Journal of Pharmacy 54, no. 2 (Nov. 2024): 215-222. https://doi.org/10.26650/IstanbulJPharm.2024.1336667


Harvard: Australian Style

Kaya Tilki, E & Engür Öztürk, S 2024, 'The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer', İstanbul Journal of Pharmacy, vol. 54, no. 2, pp. 215-222, viewed 15 Nov. 2024, https://doi.org/10.26650/IstanbulJPharm.2024.1336667


Harvard: Author-Date Style

Kaya Tilki, E. and Engür Öztürk, S. (2024) ‘The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer’, İstanbul Journal of Pharmacy, 54(2), pp. 215-222. https://doi.org/10.26650/IstanbulJPharm.2024.1336667 (15 Nov. 2024).


MLA

Kaya Tilki, Elif, and Selin Engür Öztürk. The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer.” İstanbul Journal of Pharmacy, vol. 54, no. 2, 2024, pp. 215-222. [Database Container], https://doi.org/10.26650/IstanbulJPharm.2024.1336667


Vancouver

Kaya Tilki E, Engür Öztürk S. The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer. İstanbul Journal of Pharmacy [Internet]. 15 Nov. 2024 [cited 15 Nov. 2024];54(2):215-222. Available from: https://doi.org/10.26650/IstanbulJPharm.2024.1336667 doi: 10.26650/IstanbulJPharm.2024.1336667


ISNAD

Kaya Tilki, Elif - Engür Öztürk, Selin. The proteasome inhibitor ixazomib targets epigenetic chromatin modification enzymes upregulated by m2c macrophage polarisation in lung cancer”. İstanbul Journal of Pharmacy 54/2 (Nov. 2024): 215-222. https://doi.org/10.26650/IstanbulJPharm.2024.1336667



ZAMAN ÇİZELGESİ


Gönderim02.08.2023
Kabul29.06.2024
Çevrimiçi Yayınlanma26.08.2024

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