Fucoxanthin from Laminaria japonica Targeting PANoptosis and Ferroptosis Pathways: Insights into Its Therapeutic Potential Against Ovarian Cancer.

Abstract

Ovarian cancer (OC) is a highly aggressive malignancy with a poor prognosis, necessitating novel therapeutic strategies. Fucoxanthin (FX), a marine-derived carotenoid from Laminaria japonica, has demonstrated promising anticancer potential. This study revealed that FX exerts multiple anticancer effects in OC by inhibiting cell proliferation, invasion, and migration, while inducing various forms of programmed cell death (PCD). FX triggered PANoptosis (apoptosis, necroptosis, and pyroptosis) and ferroptosis. FX treatment regulated key markers associated with PANoptosis, including apoptosis (Bcl-2, cleaved caspase-3), pyroptosis (GSDME), and necroptosis (RIPK3). Additionally, FX treatment modulated ferroptosis-related markers, such as SLC7A11 and GPX4, while increasing reactive oxygen species (ROS) and Fe²⁺ levels and disrupting mitochondrial function. Proteomic and molecular docking analyses identified AMP-activated protein kinase (AMPK) as a direct FX target, activating the AMPK/Nrf2/HMOX1 pathway to promote ferroptosis. In vivo, FX significantly reduced tumor growth in OC xenograft models, accompanied by enhanced ferroptosis marker expression. These findings demonstrate that FX induces ferroptosis through the AMPK/Nrf2/HMOX1 pathway and promotes PANoptosis via distinct mechanisms, highlighting its potential as a marine-derived therapeutic agent for OC.