ABSTRACT
Fibulin-3(FBLN3) levels are different in different types of cancers. We found that fibulin-3 was downregulated in colorectal (CRC) cells, particularly in the SW480 cell line. By comparison, transfecting SW480 cells with a lentivirus overexpressing fibulin-3 RNA could inhibit proliferation, induce G1/S arrest, and promote cell apoptosis. Fibulin-3 overexpression further suppressed the invasion and metastasis of CRC. These effects were regulated through the AKT/mTOR signaling pathway.
Subject(s)
Colorectal Neoplasms , Extracellular Matrix Proteins , Neoplasm Invasiveness , Neoplasm Metastasis , Proto-Oncogene Proteins c-akt , TOR Serine-Threonine Kinases , Apoptosis/genetics , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation/genetics , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Gene Expression , Humans , Lentivirus/genetics , Neoplasm Invasiveness/genetics , Neoplasm Metastasis/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/genetics , TOR Serine-Threonine Kinases/genetics , TransfectionABSTRACT
From the CH(2)Cl(2) extract of the sponge Hyrtios cf. erecta, collected from Fiji, two new sesterterpenes, 1 and 2, and the known compounds isodehydroluffariellolide (3), homofascaplysin A (4), and fascaplysin (5) were isolated. The structures of 1-5 were established employing 1D and 2D NMR spectroscopy and mass spectrometry. All NMR resonances of fascaplysin (5) have been unambiguously assigned. Evaluation of the biological activity of the extracts and pure compounds toward Plasmodium falciparum, Trypanosoma brucei subsp. rhodesiense, Trypanosoma cruzi, hepatitis A virus (HAV), several other microbial targets, and HIV-1-RT and p56(lck) tyrosine kinase revealed new activities for homofascaplysin (4) and fascaplysin (5), both being potently active in vitro against P. falciparum.