Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway.

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.

[Intralymphatic chemotherapy with adriamycin-adsorbing nanometric activated carbon:pharmacokinetic experiment with dogs].

OBJECTIVE: To observe the pharmacokinetics of adriamycin-adsorbing nanometric activated carbon in intralymphatic chemotherapy. METHODS: Two ml of suspension of activated carbon with the diameter of 21 nm was mixed with adriamycin 5 mg. Eighteen dogs were randomly divided into 6 equal groups. The above mentioned mixture was injected subserosally to the anterior wall of gastric antrum of the dogs. Thirty minutes, 1 h, 2 h, 1 day, and 3 days after the injection the gastroepiploic lymph nodes of the Groups 1 - 5 were obtained. And Group 6 underwent extraction of venous blood samples 5, 15, 30, 60, 120, and 240 minutes after the injection and extraction of thoracic duct fluid 5, 15, 30, 60, 120, 240, and 360 minutes after the injection. The adriamycin concentrations at different time points were determined by mass spectrometer. The lymphatic vessels and nodes at the gastric wall were observed by the naked eyes. RESULTS: Black tiny lymphatic vessels and lymph nodes were visualized around the injection areas immediately after the injection. Adriamycin content could be detected 30 min after the injection and lasted for 72 h at high levels with the peak content of (84.6 +/- 2.0) microg per gram tissue at 60 min in the perilymph node of gastroepiploic artery. The adriamycin concentration in the lymph fluid of thoracic duct reached the top level of 162.5 ng/ml 30 min after the injection, and then decreased slowly. Adriamycin could be still detected in lymph fluid 6 h after injection. No trace of adriamycin was found in the blood at any time points. CONCLUSION: The content of adriamycin can keep high and last long in the drainage of lymph node and lymph fluid in the treatment of intralymphatic chemotherapy using adriamycin-adsorbing nanometric activated carbon.