RT journal article
T1 New Insights into the Molecular Actions of Grosheimin, Costunolide, and α- and β-Cyclocostunolide on Primary Cilia Structure and Hedgehog Signaling
A1 Murillo-Pineda, Marina
A1 Martínez Miralles, Joel
A1 Medina-Calzada, Zahara
A1 Varela Montoya, Rosa María
A1 Macías Domínguez, Francisco Antonio
A1 Chinchilla Salcedo, Nuria
A1 Juárez-Soto, Álvaro
A1 Santpere, Gabriel
A1 Reales Rodríguez, Elena
A2 BiomedicinaBiotecnología y Salud Pública
A2 Química Orgánica
K1 sesquiterpene lactones
K1 primary cilium
K1 Hedgehog pathway
K1 ciliopathies
K1 tumor
K1 grosheimin
K1 costunolide
AB Sesquiterpene lactones (SLs) are plant-derived metabolites with recognized pharmacological properties. Dysfunction of the primary cilium (PC), a solitary sensory organelleessential for development, is associated with disorders such as ciliopathies and tumors.While previous studies have shown that certain SLs can alter PC structure in humanretinal cells, their influence on ciliary signaling pathways remains unclear. In this study,we examined the effect of four SLs—grosheimin, costunolide, α-cyclocostunolide (α-C),and β-cyclocostunolide (β-C)—on ciliary function in human primary fibroblasts. Usingimmunofluorescence and qPCR to assess cilia structure and Hedgehog (Hh) pathway activation, we found that grosheimin enhanced ciliogenesis without affecting Hh signaling.In contrast, costunolide, α-C, and β-C disrupted ciliary structure and suppressed the Hhpathway transcripts Gli1 and Ptch1. RNA sequencing revealed that grosheimin upregulatedgenes related to microtubule binding and ciliogenesis, whereas α-C downregulated tubulinsubunit transcripts. These findings suggest distinct molecular mechanisms through whichSLs affect ciliary structure and function. Collectively, this study highlights the potentialof specific SLs as modulators of ciliary signaling, offering promising leads for therapeuticstrategies targeting ciliopathies and tumors.
PB MDPI
SN 1422-0067
YR 2025
FD 2025-12
LK http://hdl.handle.net/10498/39539
UL http://hdl.handle.net/10498/39539
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026