Effects of Sesquiterpene Lactones on Primary Cilia Formation (Ciliogenesis)
Marina Murillo-Pineda,
Juan M. Coto-Cid,
María Romero,
Jesús G. Zorrilla,
Nuria Chinchilla,
Zahara Medina-Calzada,
Rosa M. Varela,
Álvaro Juárez-Soto,
Francisco A. Macías,
Elena Reales
Affiliations
Marina Murillo-Pineda
Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Department of Urology, University Hospital of Jerez de la Frontera, 11407 Jerez, Spain
Juan M. Coto-Cid
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), School of Science, University of Cadiz, Campus de Excelencia Internacional (ceiA3), 11510 Puerto Real, Spain
María Romero
Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Department of Urology, University Hospital of Jerez de la Frontera, 11407 Jerez, Spain
Jesús G. Zorrilla
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), School of Science, University of Cadiz, Campus de Excelencia Internacional (ceiA3), 11510 Puerto Real, Spain
Nuria Chinchilla
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), School of Science, University of Cadiz, Campus de Excelencia Internacional (ceiA3), 11510 Puerto Real, Spain
Zahara Medina-Calzada
Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Department of Urology, University Hospital of Jerez de la Frontera, 11407 Jerez, Spain
Rosa M. Varela
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), School of Science, University of Cadiz, Campus de Excelencia Internacional (ceiA3), 11510 Puerto Real, Spain
Álvaro Juárez-Soto
Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Department of Urology, University Hospital of Jerez de la Frontera, 11407 Jerez, Spain
Francisco A. Macías
Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), School of Science, University of Cadiz, Campus de Excelencia Internacional (ceiA3), 11510 Puerto Real, Spain
Elena Reales
Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Department of Urology, University Hospital of Jerez de la Frontera, 11407 Jerez, Spain
Sesquiterpene lactones (SLs), plant-derived metabolites with broad spectra of biological effects, including anti-tumor and anti-inflammatory, hold promise for drug development. Primary cilia, organelles extending from cell surfaces, are crucial for sensing and transducing extracellular signals essential for cell differentiation and proliferation. Their life cycle is linked to the cell cycle, as cilia assemble in non-dividing cells of G0/G1 phases and disassemble before entering mitosis. Abnormalities in both primary cilia (non-motile cilia) and motile cilia structure or function are associated with developmental disorders (ciliopathies), heart disease, and cancer. However, the impact of SLs on primary cilia remains unknown. This study evaluated the effects of selected SLs (grosheimin, costunolide, and three cyclocostunolides) on primary cilia biogenesis and stability in human retinal pigment epithelial (RPE) cells. Confocal fluorescence microscopy was employed to analyze the effects on primary cilia formation (ciliogenesis), primary cilia length, and stability. The effects on cell proliferation were evaluated by flow cytometry. All SLs disrupted primary cilia formation in the early stages of ciliogenesis, irrespective of starvation conditions or cytochalasin-D treatment, with no effect on cilia length or cell cycle progression. Interestingly, grosheimin stabilized and promoted primary cilia formation under cilia homeostasis and elongation treatment conditions. Thus, SLs have potential as novel drugs for ciliopathies and tumor treatment.
