Benzoquinone induces ROS-dependent mitochondria-mediated apoptosis in HL-60 cells.

Benzene exposure affects the hematopoietic system and leads to the occurrence of various types of leukemia and hematotoxicity. It has been confirmed that active metabolites of benzene, including 1,4-benzoquinone (1,4-BQ), can induce reactive oxygen species (ROS) and apoptosis in the bone marrow, and recent studies have also suggested that benzene exposure can affect mitochondrial function in both experimental animals and cell lines. However, the potential relationship among ROS production, mitochondrial damages, and subsequent apoptosis following benzene exposure has not been well studied in detail. In the present study, we utilized HL-60 cells, a well-characterized human myeloid cell line, as an in vitro model and examined the effects of 1,4-BQ on intracellular ROS formation, mitochondria damage, and the occurrence of apoptotic events with or without using the ROS scavenger N-acetyl-l-cysteine (NAC). The results demonstrated that 1,4-BQ could dose-dependently induce production of ROS and mitochondrial damage as characterized by mitochondrial membrane potential disruption, mitochondrial ultrastructure alteration, and induced apoptosis and activated caspase-3 and caspase-9. Preincubation of HL-60 cells with NAC prior to 1,4-BQ treatment could block 1,4-BQ-induced production of ROS and the occurrence of apoptosis. These results demonstrated that 1,4-BQ induced apoptosis in HL-60 cells through a ROS-dependent mitochondrial-mediated pathway.

Mn-doped Ti-based MOFs for magnetic resonance imaging-guided synergistic microwave thermal and microwave dynamic therapy of liver cancer.

Currently, precise ablation of tumors without damaging the surrounding normal tissue is still an urgent problem for clinical microwave therapy of liver cancer. Herein, we synthesized Mn-doped Ti MOFs (Mn-Ti MOFs) nanosheets by in-situ doping method and applied them for microwave therapy. Infrared thermal imaging results indicate Mn-Ti MOFs can rapidly increase the temperature of normal saline, attributing to the porous structure improving microwave-induced ion collision frequency. Moreover, Mn-Ti MOFs show higher 1O2 output than Ti MOFs under 2 W of low-power microwave irradiation due to the narrower band-gap after Mn doping. At the same time, Mn endows the MOFs with a desirable T1 contrast of magnetic resonance imaging (r2/r1 = 2.315). Further, results on HepG2 tumor-bearing mice prove that microwave-triggered Mn-Ti MOFs nearly eradicate the tumors after 14 days of treatment. Our study offers a promising sensitizer for synergistic microwave thermal and microwave dynamic therapy of liver cancer.

Ginsenoside Rk1-Loaded Manganese-Doped Hollow Titania for Enhancing Tumor Sonodynamic Therapy via Upregulation of Intracellular Reactive Oxygen Species.

Amplifying the intracellular reactive oxygen species (ROS) level remains an urgent challenge for efficient sonodynamic therapy (SDT) of tumors. Herein, by loading ginsenoside Rk1 with manganese-doped hollow titania (MHT), a Rk1@MHT sonosensitizer was conceived to strengthen the outcome of tumor SDT. The results verify that manganese-doping remarkably elevates the UV-visible absorption and decreases the bandgap energy of titania from 3.2 to 3.0 eV, which improves ROS production under ultrasonic irradiation. Immunofluorescence and Western blot analysis demonstrate that ginsenoside Rk1 can block the critical protein of the glutathione synthesis pathway, glutaminase, thus enhancing intracellular ROS by eliminating the endogenous glutathione-depleted pathway of ROS. Manganese-doping confers the nanoprobe T1-weighted MRI function (r2/r1 = 1.41). Moreover, the in vivo tests confirm that Rk1@MHT-based SDT eradicates liver cancer in tumor-bearing mice via dual upregulation of intracellular ROS production. In summary, our study provides a new strategy for designing high-performance sonosensitizer to achieve noninvasive cancer treatment.