Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells

Çınar Ayan, ilknur; Güçlü, Ebru

doi:10.30733/std.2023.01587

Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells

Ebru AVCI, (Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi, Tıp Anabilim Dalı Biyoloji, Konya, Türkiye)

İlknur ÇINAR AYAN (Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi, Tıp Anabilim Dalı Biyoloji, Konya, Türkiye)

Selçuk Tıp Dergisi

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Yıl: 2023 Cilt: 39 Sayı: 1 Sayfa Aralığı: 12 - 18 Metin Dili: İngilizce DOI: 10.30733/std.2023.01587 İndeks Tarihi: 05-05-2023

Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells

Öz:

Aim: Thyroid Hormone Receptor Interacting Protein 13 (TRIP13) is a protein involved in spindleaggregation checkpoint, which plays a role in meiotic recombination. Recent studies have revealed that TRIP13 may be a potential tumor inducer in many cancers, including glioblastoma multiforme (GBM). We aimed to investigate the anticancer activity of DCZ0415, a small molecule inhibitor of TRIP13, in U87 human GBM cells in this study . Materials and Methods: The possible anticancer effect of DCZ0415 on U87 cells was determined by cytotoxicity, colony formation, and apoptosis assays. In addition, the effects of DCZ0415 on mRNA levels of genes which were involved in apoptosis, invasion and Transforming Growth Factor-Beta (TGF-β) signaling pathway were investigated by qR T-PCR analysis. Results: DCZ0415 inhibited U87 cell proliferation in a dose and time dependent manner. The IC50 dose of DCZ0415 for 48 hours was determined as 19.77 μM in U87 cells. DCZ0415 treatment at this dose induced apoptosis and suppressed colony forming abilities of U87 cells. In addition, DCZ0415 altered mRNA levels of genes associated with apoptosis, invasion and TGF-β signaling pathway, which could lead to anticancer effects. Conclusion: DCZ0415, an inhibitor of TRIP13 which has been evaluated as a new oncogenic factor in cancer, has an anticancer effect on GBM cells. In this respect, it is thought that TRIP13 may be an important therapeutic target for GBM and DCZ0415 may be considered as an effective inhibitor that causes anticancer ef fects in GBM cells.

Anahtar Kelime:

TRIP13'ün Küçük Bir Moleküler İnhibitörü Olan DCZ0415'in, U87 İnsan Glioblastoma Multiforme Hücrelerindeki Antikanser Etkinliğinin İncelenmesi

Öz:

Amaç: Tiroid Hormon Reseptörü Etkileşimli Protein 13 (TRIP13); mayotik rekombinasyonda rol oynayan, iğ-toplanma kontrol noktasında görevli bir proteindir. Son yıllarda yapılan çalışmalar TRIP13’ün glioblastoma multiforme (GBM) de dahil olmak üzere çok sayıda kanserde potansiyel bir tümör indükleyicisi olabileceğini ortaya koymuştur. Bu çalışmada TRIP13’ün küçük bir moleküler inhibitörü olan DCZ0415’in U87 insan GBM hücrelerindeki antikanser etkinliğinin araştırılm ası amaçlandı. Gereçler ve Yöntem: DCZ0415’in U87 hücrelerindeki olası antikanser etkisi sitotoksisite analizi, koloni formasyon analizi ve apoptoz analizi ile belirlendi. Ayrıca qRT-PZR analizi ile DCZ0415’in apoptoz, invazyon ve Transforme Edici Büyüme Faktörü-Beta (TGF-β) sinyal yolağı ile ilişkili genlerin mRNA seviyeleri üzerine etkisi araştırıldı. Bulgular: DCZ0415, U87 hücre proliferasyonunu doz ve zaman bağımlı şekilde inhibe etti. U87 hücrelerinde DCZ0415’in 48 saat için IC50 dozu 19,77 μM olarak belirlendi. Bu dozda DCZ0415 uygulaması U87 hücrelerinde apoptozu indükledi ve hücrelerin koloni oluşturma yeteneklerini baskıladı. Ayrıca DCZ0415 apoptoz, invazyon ve TGF-β sinyal yolağı ile ilişkili genlerin mRNA seviyelerini antikanser etkiye yol açabilecek şekilde değiştirdi. Sonuç: Kanserde yeni bir onkogenik faktör olarak değerlendirilen TRIP13’ün bir inhibitörü olan DCZ0415, GBM hücrelerinde antikanser etkiye sahiptir. Bu açıdan, TRIP13’ün GBM için önemli bir terapötik hedef olabileceği ve DCZ0415’in GBM hücrelerinde antikanser etkiye yol açan etkili bir inhibitör olarak değerlendirilebileceği düşünülmektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Güçlü E, Çınar Ayan i (2023). Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. , 12 - 18. 10.30733/std.2023.01587
Chicago	Güçlü Ebru,Çınar Ayan ilknur Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. (2023): 12 - 18. 10.30733/std.2023.01587
MLA	Güçlü Ebru,Çınar Ayan ilknur Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. , 2023, ss.12 - 18. 10.30733/std.2023.01587
AMA	Güçlü E,Çınar Ayan i Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. . 2023; 12 - 18. 10.30733/std.2023.01587
Vancouver	Güçlü E,Çınar Ayan i Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. . 2023; 12 - 18. 10.30733/std.2023.01587
IEEE	Güçlü E,Çınar Ayan i "Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells." , ss.12 - 18, 2023. 10.30733/std.2023.01587
ISNAD	Güçlü, Ebru - Çınar Ayan, ilknur. "Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells". (2023), 12-18. https://doi.org/10.30733/std.2023.01587

APA	Güçlü E, Çınar Ayan i (2023). Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. Selçuk Tıp Dergisi, 39(1), 12 - 18. 10.30733/std.2023.01587
Chicago	Güçlü Ebru,Çınar Ayan ilknur Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. Selçuk Tıp Dergisi 39, no.1 (2023): 12 - 18. 10.30733/std.2023.01587
MLA	Güçlü Ebru,Çınar Ayan ilknur Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. Selçuk Tıp Dergisi, vol.39, no.1, 2023, ss.12 - 18. 10.30733/std.2023.01587
AMA	Güçlü E,Çınar Ayan i Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. Selçuk Tıp Dergisi. 2023; 39(1): 12 - 18. 10.30733/std.2023.01587
Vancouver	Güçlü E,Çınar Ayan i Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells. Selçuk Tıp Dergisi. 2023; 39(1): 12 - 18. 10.30733/std.2023.01587
IEEE	Güçlü E,Çınar Ayan i "Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells." Selçuk Tıp Dergisi, 39, ss.12 - 18, 2023. 10.30733/std.2023.01587
ISNAD	Güçlü, Ebru - Çınar Ayan, ilknur. "Investigation of the Anticancer Activity of DCZ0415, a Small Molecular Inhibitor of TRIP13, in U87 Human Glioblastoma Multiforme Cells". Selçuk Tıp Dergisi 39/1 (2023), 12-18. https://doi.org/10.30733/std.2023.01587