We previously reported that smenospongine, a sesquiterpene aminoquinone isolated from the marine sponge Dactylospongia elegans, showed antiproliferative or cytotoxic activities on leukemia cells. In this study, we investigated the effect of smenospongine on solid tumors. Since angiogenesis is well known to be closely involved in growth and metastasis of solid tumors, the antiangiogenic effect of smenospongine was determined. We found that smenospongine inhibited proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVEC). Moreover, the inhibitory activity of smenospongine on growth of solid tumor cells was investigated. Smenospongine inhibited the growth of 39 human solid cancer cells in vitro, with a mean Log GI₅₀ value of −5.55. In conclusion, smenospongine exhibits antitumor activity on solid tumors via two mechanisms, an antiangiogenic effect on endothelial cells and direct inhibition of growth of tumor cells.

Tumor metastasis is the main cause of lethality of prostate cancer, because conventional therapies like surgery and hormone treatment rarely work at this stage. Tumor cell migration, invasion and adhesion are necessary processes for metastasis. By providing nutrition and an escape route from the primary site, angiogenesis is also required for tumor metastasis. Phosphatidylinositol 3-kinases (PI3Ks) are well known to play important roles in tumorigenesis as well as metastasis. ZSTK474 is a specific PI3K inhibitor developed for solid tumor therapy. In the present report, antimetastatic activities of ZSTK474 were investigated in vitro by determining the effects on the main metastatic processes. ZSTK474 exhibited inhibitory effects on migration, invasion and adhesive ability of prostate cancer PC3 cells. Furthermore, ZSTK474 inhibited phosphorylation of Akt substrate-Girdin, and the secretion of matrix metalloproteinase (MMP), both of which were reported to be closely involved in migration and invasion. On the other hand, ZSTK474 inhibited the expression of HIF-1α and the secretion of vascular endothelial growth factor (VEGF), suggesting its potential antiangiogenic activity on PC3 cells. Moreover, we demonstrated the antiangiogenesis by determining the effect of ZSTK474-reduced VEGF on tube formation of human umbilical vein endothelial cells (HUVECs). In conclusion, ZSTK474 was demonstrated to have potential in vitro antimetastatic effects on PC3 cells via dual mechanisms: inhibition of metastatic processes including cell migration, invasion and adhesion, and antiangiogenesis via blockade of VEGF secretion.

A novel triterpene, 2α,3β,20,23-tetrahydroxyurs-28-oic acid (1), was isolated from the aerial part of Centella asiatica. Its structure was elucidated by spectroscopic methods, including 2D-NMR spectra. It displayed no activity against Hela and A549 cell lines at concentrations of 10 and 30 μg/mL, respectively.