Faculty of Medicine, Medical Biology Department, Ege University, Izmir, Turkey.
Vocational School of Health Sciences, Near East University, Nicosia, North Cyprus.
Nutr Cancer. 2022;74(10):3679-3691. doi: 10.1080/01635581.2022.2077969. Epub 2022 May 24.
is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose ∼5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G/G, S phases accompanied by regulations in and expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML.
因其具有抗炎、抗菌和抗氧化特性，在民间医学中被使用。帕纳替尼是一种治疗慢性髓性白血病（CML）的有效酪氨酸激酶抑制剂，但其具有严重的副作用。因此，我们旨在确定一种新的草药联合治疗方法，不仅可以提高抗白血病疗效，还可以降低帕纳替尼在靶向 CML 细胞中的剂量。用甲醇（OSM）提取，并用植物化学筛选试验测定其次生代谢产物。通过 WST-1 测定法测定 OSM 对 K562 细胞的细胞毒性作用。用中效方程分析帕纳替尼和 OSM（p-OSM）的组合。通过流式细胞术研究细胞凋亡、增殖和细胞周期。通过 qRT-PCR 评估与细胞周期相关的基因表达。含有萜类化合物、类黄酮、单宁和蒽的 OSM 对 K562 细胞具有细胞毒性作用。p-OSM 的中效作用被发现为协同作用；OSM 将帕纳替尼的剂量降低了约 5 倍。p-OSM 提高了帕纳替尼的促凋亡和抗增殖活性。一致地，p-OSM 阻断了细胞周期在 G/G 和 S 期的进展，伴随着 和 表达的调节。OSM 通过诱导细胞凋亡、抑制增殖和细胞周期协同增强帕纳替尼的抗白血病活性。因此，OSM 可能为治疗 CML 患者提供一种潜在的策略。
