Bilajac Esma, Mahmutović Lejla, Glamočlija Una, Osmanović Amar, Hromić-Jahjefendić Altijana, Tambuwala Murtaza M, Suljagić Mirza
Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnička cesta 15, 71000 Sarajevo, Bosnia and Herzegovina.
Faculty of Pharmacy, University of Sarajevo, Zmaja od Bosne 8, 71000 Sarajevo, Bosnia and Herzegovina.
Metabolites. 2022 Dec 30;13(1):58. doi: 10.3390/metabo13010058.
Chronic myeloid leukemia (CML) is a myeloproliferative haematological malignancy characterized by constitutive activation of BCR-ABL1 tyrosine kinase in the majority of patients. BCR-ABL1 expression activates signaling pathways involved in cell proliferation and survival. Current treatment options for CML include tyrosine kinase inhibitors (TKI) with resistance as a major issue. Various treatment options for overcoming resistance are being investigated. Among them, phytochemical curcumin could play an important role. Curcumin has been found to exhibit anti-cancerous effects in various models, including CML, through regulation of multiple molecular signaling pathways contributing to tumorigenesis. We have evaluated curcumin's effects on imatinib-sensitive LAMA84S and K562, as well as imatinib-resistant LAMA84R cell lines. Our results indicate a significant dose-dependent decrease in cell viability and proliferation of imatinib-sensitive and imatinib-resistant cell lines after curcumin treatment. Suppression of key signaling molecules regulating metabolic and proliferative events, such as Akt, P70S6K and NF-kB, was observed. Increased expression of caspase-3 suggests the potential pro-apoptotic effect of curcumin in the imatinib-resistant CML model. Additional in silico molecular docking studies revealed binding modes and affinities of curcumin with different targets and the results are in accordance with in vitro findings. Altogether, these results indicate the potential role of curcumin in the treatment of CML.
慢性髓性白血病（CML）是一种骨髓增殖性血液恶性肿瘤，大多数患者的特征是BCR-ABL1酪氨酸激酶的组成性激活。BCR-ABL1表达激活参与细胞增殖和存活的信号通路。目前CML的治疗选择包括酪氨酸激酶抑制剂（TKI），但耐药性是一个主要问题。正在研究各种克服耐药性的治疗选择。其中，植物化学物质姜黄素可能发挥重要作用。已发现姜黄素在包括CML在内的各种模型中通过调节多种促成肿瘤发生的分子信号通路而表现出抗癌作用。我们评估了姜黄素对伊马替尼敏感的LAMA84S和K562以及伊马替尼耐药的LAMA84R细胞系的影响。我们的结果表明，姜黄素处理后，伊马替尼敏感和耐药细胞系的细胞活力和增殖均出现显著的剂量依赖性下降。观察到关键信号分子如Akt、P70S6K和NF-κB对代谢和增殖事件的调节受到抑制。caspase-3表达增加表明姜黄素在伊马替尼耐药的CML模型中具有潜在的促凋亡作用。额外的计算机分子对接研究揭示了姜黄素与不同靶点的结合模式和亲和力，结果与体外研究结果一致。总之，这些结果表明姜黄素在CML治疗中的潜在作用。
