j. fac. pharm. ankara Journal of Faculty of Pharmacy of Ankara University 1015-3918 2564-6524 Ankara University 10.33483/jfpau.1286359 Pharmacology and Pharmaceutical Sciences Eczacılık ve İlaç Bilimleri KOENZİM Q0 İNSAN KRONİK MYELOİD LÖSEMİ K562 HÜCRELERİNİN PROLİFERASYONUNU ENGELLER VE MAPK VE AKT SİNYAL YOLAKLARINI MODÜLE EDER COENZYME Q0 INHIBITS CELL PROLIFERATION AND MODULATES MAPK AND AKT SIGNALLING PATHWAYS IN HUMAN CHRONIC MYELOID LEUKEMIA K562 CELLS https://orcid.org/0000-0002-8490-6293 Kaya Sezginer Ecem ANKARA ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, TEMEL ECZACILIK BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI https://orcid.org/0000-0002-8951-5478 Yaprak Ali ANKARA ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, TEMEL ECZACILIK BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI https://orcid.org/0000-0002-2482-0359 Karabay Arzu Zeynep ANKARA ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, TEMEL ECZACILIK BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI 09 20 2023 47 3 761 769 04 21 2023 05 17 2023 Copyright © 1971, Journal of Faculty of Pharmacy of Ankara University 1971 Journal of Faculty of Pharmacy of Ankara University

Amaç: Bu çalışma, insan kronik miyeloid lösemi K562 hücre hattında koenzim Q0'ın (CoQ0) antiproliferatif ve proapoptotik etkilerini değerlendirmiştir.Gereç ve Yöntem: CoQ0'ın insan kronik miyeloid lösemi K562 hücre hattındaki sitotoksik etkisi, MTT testi ile belirlendi. Kaspaz-3 aktivitesi, apoptozis, MAPK ve AKT sinyal yolağı ile ilişkili proteinlerin ekspresyonu sırasıyla enzimatik analiz ve western blot analizi ile belirlendi. Sonuç ve Tartışma: Sonuçlar, CoQ0’ın K562 hücre canlılığını 5 μM ve daha yüksek konsantrasyonlarda inhibe ettiğini ve Bax protein ekspresyonunu, 12.5 μM konsantrasyonunda önemli ölçüde azalttığını göstermiştir, ancak CoQ0 kaspaz 3 aktivitesini ve Bcl-2 protein ekspresyonunu önemli ölçüde etkilemedi. p-c-Raf (Ser259) protein ekspresyonu, 12.5 μM CoQ0'da önemli ölçüde azaldı. K562 hücre hattında, 10 μM CoQ0, p38 MAPK'nın fosforilasyonunu önemli ölçüde indükledi ve 12,5 μM CoQ0, p-ERK1/2 protein ekspresyonunda anlamlı olmayan bir azalmaya neden oldu. İlginç bir şekilde, 12.5 μM CoQ0 K562 hücrelerinde Akt (Ser473) fosforilasyonu azalttı, ancak p-Akt (Thr308) protein ekspresyonunda gruplar arasında herhangi bir farklılık gözlenmedi. Sonuç olarak, CoQ0, K562 hücrelerinin proliferasyonunu inhibe etti ve c-Raf (Ser259), Akt (Ser473) fosforilasyonunu baskıladı, ancak ERK1/2 fosforilasyonuna etki etmedi. CoQ0'ın antikanser etkisinin altında yatan moleküler mekanizmalara yeni bakış açıları sağlamak ve kronik miyeloid lösemi tedavi stratejilerini geliştirmek için daha fazla araştırmaya hala ihtiyaç bulunmaktadır.

Objective: This study evaluated the antiproliferative and pro-apoptotic effects of coenzyme Q0 (CoQ0) in human chronic myeloid leukemia K562 cell line.Material and Method: The cytotoxic effect of CoQ0 on human chronic myeloid leukemia cell line, K562 was determined by MTT test. The activity of caspase-3, expression of proteins involved in apoptosis, MAPK and AKT signaling pathways were determined with enzymatic assay and western blot analysis, respectively.Result and Discussion: Results showed that CoQ0 inhibited cell viability of K562 cells at 5 μM and higher concentrations and Bax protein expression was significantly decreased at 12.5 μM concentration of CoQ0. However, CoQ0 did not significantly affect caspase 3 activity and Bcl-2 protein expression. p-c-Raf (Ser259) protein expression was significantly decreased at 12.5 μM of CoQ0. Treatment with 10 μM of CoQ0 induced significantly phosphorylation of p38 MAPK and 12.5 μM CoQ0 caused a nonsignificant decrease in p-ERK1/2 protein expression in K562 cell line. Interestingly, in K562 cells, phosphorylation of Akt (Ser473) was diminished at 12.5 μM of CoQ0, with no change observed in p-Akt (Thr308) protein expression among groups. In conclusion, CoQ0 inhibited cell proliferation and suppressed phosphorylation of c-Raf (Ser259), Akt (Ser473), but not ERK1/2 in K562 cells. There is still a need for new insights into the anticancer mechanisms of CoQ0 and develop treatment strategies for chronic myeloid leukemia.

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