The geodiamolide H, derived from Brazilian sponge Geodia corticostylifera, regulates actin cytoskeleton, migration and invasion of breast cancer cells cultured in three-dimensional environment.
We are investigating effects of the depsipeptide geodiamolide H, isolated from the Brazilian sponge Geodia corticostylifera, on cancer cell lines grown in 3D environment. As shown previously geodiamolide H disrupts actin cytoskeleton in both sea urchin eggs and breast cancer cell monolayers. We used a normal mammary epithelial cell line MCF 10A that in 3D assay results formation of polarized spheroids. We also used cell lines derived from breast tumors with different degrees of differentiation: MCF7 positive for estrogen receptor and the Hs578T, negative for hormone receptors. Cells were placed on top of Matrigel. Spheroids obtained from these cultures were treated with geodiamolide H. Control and treated samples were analyzed by light and confocal microscopy. Geodiamolide H dramatically affected the poorly differentiated and aggressive Hs578T cell line. The peptide reverted Hs578T malignant phenotype to polarized spheroid-like structures. MCF7 cells treated by geodiamolide H exhibited polarization compared to controls. Geodiamolide H induced striking phenotypic modifications in Hs578T cell line and disruption of actin cytoskeleton. We investigated effects of geodiamolide H on migration and invasion of Hs578T cells. Time-lapse microscopy showed that the peptide inhibited migration of these cells in a dose-dependent manner. Furthermore invasion assays revealed that geodiamolide H induced a 30% decrease on invasive behavior of Hs578T cells. Our results suggest that geodiamolide H inhibits migration and invasion of Hs578T cells probably through modifications in actin cytoskeleton. The fact that normal cell lines were not affected by treatment with geodiamolide H stimulates new studies towards therapeutic use for this peptide.
Freitas
Vanessa M
VM
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. vfreitas@usp.br
Rangel
Marisa
M
Bisson
Letícia F
LF
Jaeger
Ruy G
RG
Machado-Santelli
Gláucia M
GM
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D018929:Cell Culture Techniques; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity; D048430:Cell Shape; D003094:Collagen / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects*; D047630:Depsipeptides / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D047231:Geodia; D006801:Humans; D007797:Laminin / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000199:Actins; D001672:Biocompatible Materials; D047630:Depsipeptides; D004338:Drug Combinations; D007797:Laminin; D019384:Nucleic Acid Synthesis Inhibitors; D011509:Proteoglycans; C514602:geodiamolide H; C059485:matrigel; D015638:Cytochalasin D; D003094:Collagen