Department of Natural Sciences, Faculty of Science and Technology, Middlesex University, London NW4 4BT, UK.
Mol Med Rep. 2018 Mar;17(3):4524-4530. doi: 10.3892/mmr.2018.8396. Epub 2018 Jan 8.
Baicalein (BL), a potential cancer chemopreventative flavone, has been reported to inhibit cancer cell growth by inducing apoptosis and causing cell cycle arrest in various human cancer cell models. Delivery of BL via nanoliposomes has been shown to improve its oral bioavailability and long‑circulating property in vivo. However, the role of BL in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms has yet to be elucidated. In the present study, BL was formulated into liposomes with different sizes to improve its solubility and stability. The cytotoxic and pro‑apoptotic effects of free BL and liposomal BL were also evaluated. The results demonstrated that 100 nm liposomes were the most stable formulation when compared with 200 and 400 nm liposomes. Liposomal BL inhibited K562 cell growth as efficiently as free BL (prepared in DMSO), indicating that the liposome may be a potential vehicle to deliver BL for the treatment of CML. Flow cytometry analysis showed that there was significant (P<0.005) cell cycle arrest in the sub‑G1 phase (compared with vehicle control), indicating cell apoptosis following 20 µM liposomal BL or free BL treatment of K562 cells for 48 h. The induction of cell apoptosis by all BL preparations was further confirmed through the staining of treated cells with Annexin V‑fluorescein isothiocyanate/propidium iodide. A significant increase in reactive oxygen species (ROS) gene-ration was observed in free BL and liposomal BL treated cells, with a higher level of ROS produced from those treated with free BL. This indicated that cell apoptosis induced by BL may be via ROS generation and liposome delivery may further extend the effect through its long‑circulating property.
白杨素（BL）是一种有潜力的癌症化学预防黄酮类化合物，据报道，它通过诱导细胞凋亡和使各种人类癌细胞模型中的细胞周期停滞来抑制癌细胞生长。通过纳米脂质体递送来 BL 已被证明可以提高其在体内的口服生物利用度和长循环特性。然而，BL 抑制人慢性髓性白血病（CML）K562 细胞生长的作用及其潜在机制尚未阐明。在本研究中，将 BL 制成不同大小的脂质体以提高其溶解度和稳定性。还评估了游离 BL 和脂质体 BL 的细胞毒性和促凋亡作用。结果表明，与 200nm 和 400nm 脂质体相比，100nm 脂质体是最稳定的制剂。脂质体 BL 抑制 K562 细胞生长的效率与游离 BL（在 DMSO 中制备）相当，表明脂质体可能是递送 BL 用于治疗 CML 的潜在载体。流式细胞术分析表明，与载体对照组相比，亚 G1 期（sub-G1 phase）有明显的细胞周期停滞（P<0.005），表明 K562 细胞用 20µM 脂质体 BL 或游离 BL 处理 48 小时后发生细胞凋亡。用 Annexin V-荧光素异硫氰酸酯/碘化丙啶对处理过的细胞进行染色，进一步证实了所有 BL 制剂均可诱导细胞凋亡。在游离 BL 和脂质体 BL 处理的细胞中观察到活性氧（ROS）基因的显著增加（P<0.005），用游离 BL 处理的细胞产生的 ROS 水平更高。这表明 BL 诱导的细胞凋亡可能是通过 ROS 生成，而脂质体递送可能通过其长循环特性进一步延长其作用。
