Dehydrocostuslactone Suppresses Angiogenesis In Vitro and In Vivo through Inhibition of Akt/GSK-3β and mTOR Signaling Pathways

The traditional Chinese medicine component dehydrocostuslactone (DHC) isolated from Saussurea costus (Falc.) Lipschitz, has been shown to have anti-cancer activity. Angiogenesis is an essential process in the growth and progression of cancer. In this study, we demonstrated, for the first time, the anti-angiogenic mechanism of action of DHC to be via the induction of cell cycle progression at the G0/G1 phase due to abrogation of the Akt/glycogen synthase kinase-3β (GSK-3β)/cyclin D1 and mTOR signaling pathway. First, we demonstrated that DHC has an anti-angiogenic effect in the matrigel-plug nude mice model and an inhibitory effect on human umbilical vein endothelial cell (HUVEC) proliferation and capillary-like tube formation in vitro. DHC caused G0/G1 cell cycle arrest, which was associated with the down-regulation of cyclin D1 expression, leading to the suppression of retinoblastoma protein phosphorylation and subsequent inhibition of cyclin A and cdk2 expression. With respect to the molecular mechanisms underlying the DHC-induced cyclin D1 down-regulation, this study demonstrated that DHC significantly inhibits Akt expression, resulting in the suppression of GSK-3β phosphorylation and mTOR expression. These effects are capable of regulating cyclin D1 degradation, but they were significantly reversed by constitutively active myristoylated (myr)-Akt. Furthermore, the abrogation of tube formation induced by DHC was also reversed by overexpression of Akt. And the co-treatment with LiCl and DHC significantly reversed the growth inhibition induced by DHC. Taken together, our study has identified Akt/GSK-3β and mTOR as important targets of DHC and has thus highlighted its potential application in angiogenesis-related diseases, such as cancer

Caribbean-Wide, Long-Term Study of Seagrass Beds Reveals Local Variations, Shifts in Community Structure and Occasional Collapse

The CARICOMP monitoring network gathered standardized data from 52 seagrass sampling stations at 22 sites (mostly Thalassia testudinum-dominated beds in reef systems) across the Wider Caribbean twice a year over the period 1993 to 2007 (and in some cases up to 2012). Wide variations in community total biomass (285 to >2000 g dry m−2) and annual foliar productivity of the dominant seagrass T. testudinum (2000 g dry m−2) were found among sites. Solar-cycle related intra-annual variations in T. testudinum leaf productivity were detected at latitudes > 16°N. Hurricanes had little to no long-term effects on these well-developed seagrass communities, except for 1 station, where the vegetation was lost by burial below ∼1 m sand. At two sites (5 stations), the seagrass beds collapsed due to excessive grazing by turtles or sea-urchins (the latter in combination with human impact and storms). The low-cost methods of this regional-scale monitoring program were sufficient to detect long-term shifts in the communities, and fifteen (43%) out of 35 long-term monitoring stations (at 17 sites) showed trends in seagrass communities consistent with expected changes under environmental deterioration.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR