Phylloroseobilin impairs tumor cell migration and vascular network stability via cytoskeletal destabilization

Phyllobilins (PBs) are linear tetrapyrroles and represent the only known bilin family originating from chlorophyll rather than heme. Although colorless phylloleucobilins have long been regarded as the predominant chlorophyll metabolites, recent evidence indicates that colored phylloxanthobilins (PxBs) and phylloroseobilins (PrBs) are more widespread and structurally diverse than previously assumed. Here, we employed UHPLC-VWD-HRMS² in combination with feature-based molecular networking (FBMN) to systematically search for PrBs in plant extracts known to contain PxBs, revealing that both PB-types co-occur in several plant extracts. Functionally, we show that a PrB from Cercidiphyllum japonicum inhibits directed migration of T24 cancer cells in a Boyden chamber assay and disrupts endothelial tube stability in HUVEC while leaving extracellular matrix remodeling largely unaffected. These findings establish PrB as an actin-targeting bilin and highlight PBs as a previously overlooked natural-product scaffold for modulating the actin cytoskeleton in the context of cancer progression and angiogenesis.