Kaempferide Inhibits the Proliferation and Invasion and Induces Ferroptosis in Melanoma by Inactivating Wnt/β-Catenin...

Area of Science:

• Oncology
• Biochemistry
• Pharmacology

Background:

• Melanoma is an aggressive skin cancer with high lethality.
• Kaempferide (KF), a natural flavonoid, exhibits anti-cancer properties in various cancers, but its effect on melanoma is largely unknown.

Purpose of the Study:

• To investigate the anti-cancer effects and underlying mechanisms of Kaempferide (KF) on melanoma.
• To explore KF's impact on melanoma cell proliferation, invasion, ferroptosis, and the Wnt/β-catenin signaling pathway.

Main Methods:

• In vitro studies utilized cell counting kit-8, Transwell assays, iron measurements, ROS level determination, and Western blotting on A375 and A2085 melanoma cells.
• In vivo studies involved xenografted mice with A375 cells, employing immunohistochemistry and Western blot analysis.
• Key molecular targets and pathways, including epithelial-mesenchymal transition markers, ferroptosis indicators (Fe2+, ROS, xCT, GPX4), and the Wnt/β-catenin pathway (GSK3β, c-Myc, β-catenin), were assessed.

Main Results:

• KF decreased N-cadherin expression, invasion, and cell survival while increasing E-cadherin expression in melanoma cells.
• KF treatment elevated intracellular iron (Fe2+) and reactive oxygen species (ROS) levels, suppressed xCT and GPX4 expression, indicating ferroptosis induction.
• KF inhibited the Wnt/β-catenin pathway by reducing p-GSK3β, c-Myc, and active-β-catenin levels; LiCl treatment reversed these effects.
• In vivo, KF reduced tumor weight and volume and modulated key protein expressions consistent with in vitro findings.

Conclusions:

• Kaempferide (KF) inhibits melanoma progression by attenuating proliferation and invasion and inducing ferroptosis.
• The anti-melanoma effects of KF are mediated through the suppression of the Wnt/β-catenin signaling pathway.
• KF demonstrates significant therapeutic potential for melanoma treatment.