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

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Tongue cancer presents a significant global health challenge.
• Identifying novel therapeutic agents with distinct mechanisms of action is crucial for improving treatment outcomes.
• Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a promising target in cancer therapy.

Purpose of the Study:

• To investigate the mechanism by which fucoxanthin induces ferroptosis in tongue cancer cells.
• To evaluate the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells.
• To explore the potential of fucoxanthin as a novel therapeutic agent for tongue cancer.

Main Methods:

• Cell viability was assessed using MTT assays.
• Levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured.
• Gene and protein expression of key ferroptosis-related molecules (GPX4, Nrf2, Keap1, SLC7A11, TFR1, p53, HO-1) were analyzed via RT-qPCR and Western blotting.
• Molecular docking was employed to predict binding interactions.

Main Results:

• Fucoxanthin significantly inhibited SCC-25 cell activity in a dose- and time-dependent manner.
• Treatment with fucoxanthin led to decreased MMP, GSH, and SOD levels, alongside increased ROS, MDA, and total iron.
• Fucoxanthin downregulated the expression of Keap1, GPX4, Nrf2, and HO-1, while upregulating TFR1 and p53 expression.
• Molecular docking confirmed favorable binding energies between fucoxanthin and key proteins involved in ferroptosis.

Conclusions:

• Fucoxanthin acts as a novel ferroptosis inducer in tongue squamous carcinoma cells (SCC-25).
• The mechanism involves modulation of oxidative stress, iron metabolism, and key ferroptosis regulatory proteins.
• Fucoxanthin demonstrates significant potential as a therapeutic agent for tongue cancer.