RESUMO
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.
Assuntos
Ferroptose , Heme Oxigenase-1 , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Xantofilas , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Ferroptose/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/química , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Linhagem Celular Tumoral , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Receptores da Transferrina/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Superóxido Dismutase/metabolismo , Regulação para Baixo/efeitos dos fármacos , Antígenos CDRESUMO
Studies have shown that Sargassum fusiforme and its extracts are effective herbal treatments for leukemia. We previously found that a polysaccharide from Sargassum fusiforme, SFP 2205, stimulated apoptosis in human erythroleukemia (HEL) cells. However, the structural characterization and antitumoral mechanisms of SFP 2205 remain uncertain. Here, we studied the structural characteristics and anticancer mechanisms of SFP 2205 in HEL cells and a xenograft mouse model. The results demonstrated that SFP 2205, with a molecular weight of 41.85 kDa, consists of mannose, rhamnose, galactose, xylose, glucose, and fucose with monosaccharides composition of 14.2%, 9.4%, 11.8%, 13.7%, 11.0%, and 38.3%, respectively. On animal assays, SFP 2205 significantly inhibited growth of HEL tumor xenografts with no discernible toxicity to normal tissues. Western blotting showed that SFP 2205 therapy improved Bad, Caspase-9, and Caspase-3 protein expression, and ultimately induced HEL tumor apoptosis, indicating mitochondrial pathway involvement. Furthermore, SFP 2205 blocked the PI3K/AKT signaling pathway and 740 Y-P, an activator of the PI3K/AKT pathway, rescued the effects of SFP 2205 on HEL cell proliferation and apoptosis. Overall, SFP 2205 may be a potential functional food additive or adjuvant for preventing or treating leukemia.
