{Reference Type}: Journal Article
{Title}: Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple-Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha.
{Author}: Sperlich J;Teusch N;
{Journal}: Molecules
{Volume}: 23
{Issue}: 8
{Year}: Aug 2018 10
{Factor}: 4.927
{DOI}: 10.3390/molecules23081992
{Abstract}: Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities, including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple-negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as-yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that the antiproliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited the invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a coculture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, and the production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to a monoculture. Notably, pseudopterosin indicated to block cytokine elevation, representing key players in tumor progression in the coculture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.