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.