Liposome‑delivered baicalein induction of myeloid leukemia K562 cell death via reactive oxygen species generation

Abstract

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) generation 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.

Advances in Anti-Cancer Activities of Flavonoids in Scutellariae radix: Perspectives on Mechanism

“…Based on this theoretical knowledge, Liu and colleagues provided evidence that baicalein, as a pro-oxidant, induced the mitochondrial pathway-dependent apoptosis and selective death of MCF-7 cells through mobilizing intracellular copper and forming a baicalein-copper complex, which was able to engage in redox cycling and lead to ROS overload [ 21 ]. These findings were further confirmed by a recent study, in which authors evaluated the cytotoxic and pro-apoptotic effects in myeloid leukemia K562 cells and found that all baicalein preparations induced the accumulation of ROS in K562 cells [ 22 ]. In addition, ROS also functions as the signaling molecule to activate the AMP-activated protein kinase (AMPK) pathway, thus inhibiting cell proliferation and tumorigenesis [ 23 ].…”

Novel Liposomal Formulation of Baicalein for the Treatment of Pancreatic Ductal Adenocarcinoma: Design, Characterization, and Evaluation

“…As we have mentioned, BAI is reported as a potentially excellent weapon against PDAC. However, this potential is strictly limited by its very low water solubility (0.054 mg/mL) [ 59 ], which means there is no possibility to achieve a significant biological impact after administration. There have already been reports of BAI encapsulation into liposomes, but none of them were tested against pancreatic cancer cells or tissues.…”

Influence of Cucurbiturils on the Production of Reactive Oxygen Species by T- and B-Lymphocytes, Platelets and Red Blood Cells

“…Different ROS levels into tumor lines can lead to their death or malignancy due effecting of the various molecules [ 43 , 44 , 45 ]. These molecules either increase or decrease ROS levels; therefore, it was necessary to research effect of cucurbiturils on ROS production by different tumor cells.…”