Ecem KAYA SEZGİNER, Ali YAPRAK, Arzu Zeynep KARABAY

KOENZİM Q0 İNSAN KRONİK MYELOİD LÖSEMİ K562 HÜCRELERİNİN PROLİFERASYONUNU ENGELLER VE MAPK VE AKT SİNYAL YOLAKLARINI MODÜLE EDER

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.

Anahtar Kelimeler:

Koenzim Q0, kronik miyeloid lösemi, K562

COENZYME Q0 INHIBITS CELL PROLIFERATION AND MODULATES MAPK AND AKT SIGNALLING PATHWAYS IN HUMAN CHRONIC MYELOID LEUKEMIA K562 CELLS

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.

Keywords:

Chronic myeloid leukemia, coenzyme Q0, K562,

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