One new pentacyclic sesterterpene, hippospongide A (1), and one new scalarane sesterterpenoid, hippospongide B (2), along with six previously reported known scalarane–type sesterterpenes (3–8), were isolated from a sponge Hippospongiasp. The structures of these compounds were elucidated on the basis of their spectroscopic data and comparison of the NMR data with those of known analogues. These metabolites are the first pentacyclic sesterterpene and scalarane-type sesterterpenes to be reported from this genus. Compounds 3–5 exhibited significant cytotoxicity against DLD-1, HCT-116, T-47D and K562 cancer cell lines.
The effects of naturally acidified seawater on shell traits were quantified through the comparison of dove snails (Family: Columbellidae) Anachis misera from vent environments with Euplica sp. from non-vent sites in northeastern Taiwan. Samples of A. misera were collected around a shallow vent (24.8341° N, 121.96191° E), which included the east, south, southwest, and northwest sites. An absence of Anachis snails was found in the most acidic north site (pH 7.19–7.25). Based on the similarities of protein expression profiles, the Anachis snails were classified into two groups, i.e., V-South (pH 7.78–7.82) and V-Rest (pH 7.31–7.83). Comparing their shell traits to the non-vent Euplica sp. from Da-xi (DX) and Geng-fang (GF) (pH 8.1–8.2), a difference in shell shape (shell width : shell length) was found, with the populations having more globular shells than the non-vent ones. The means of shell width were significantly different among sites (p < 0.01), with a descending order of GF > DX > V-South and V-Rest. The relationships of shell length to total weight were curvilinear for both Anachis and Euplica snails. The logarithmically transformed slopes differed significantly among sites, and the mean body weight of the GF population was greater than that of the others (p < 0.01). Positive correlations between shell length and shell thickness of body whorl (T1) and penultimate whorl (T2) were only observed in non-vent GF and DX populations. Anachis snails from vent sites were thinner in T1 and T2 compared to the Euplica snails from non-vent sites (p < 0.05). Within each vent group, shell thickness between T1 and T2 was insignificantly different. Between vent groups, T1 and T2 from V-Rest showed a decrease of 10.6 and 10.2%, respectively, compared to V-South ones. The decrease of T1 and T2 between vent Anachis snails and non-vent Euplica snails was as great as 55.6 and 29.0%, respectively. This was the first study to compare snail's morphological traits under varying shallow-vent stresses with populations previously classified by biochemical responses. Overall, the shallow-vent-based findings provide additional information from subtropics on the effects of acidified seawater on gastropod snails in natural environments.
A dibromotyrosine derivative, (1′R,5′S,6′S)-2-(3′,5′-dibromo-1′,6′-dihydroxy-4′-oxocyclohex-2′-enyl) acetonitrile (DT), was isolated from the sponge Pseudoceratina sp., and was found to exhibit a significant cytotoxic activity against leukemia K562 cells. Despite the large number of the isolated bromotyrosine derivatives, studies focusing on their biological mechanism of action are scarce. In the current study we designed a set of experiments to reveal the underlying mechanism of DT cytotoxic activity against K562 cells. First, the results of MTT cytotoxic and the annexin V-FITC/PI apoptotic assays, indicated that the DT cytotoxic activity is mediated through induction of apoptosis. This effect was also supported by caspases-3 and -9 activation as well as PARP cleavage. DT induced generation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential (MMP) as indicated by flow cytometric assay. The involvement of ROS generation in the apoptotic activity of DT was further corroborated by the pretreatment of K562 cells with N-acetyl-cysteine (NAC), a ROS scavenger, which prevented apoptosis and the disruption of MMP induced by DT. Results of cell-free system assay suggested that DT can act as a topoisomerase II catalytic inhibitor, unlike the clinical anticancer drug, etoposide, which acts as a topoisomerase poison. Additionally, we found that DT treatment can block IKK/NFκB pathway and activate PI3K/Akt pathway. These findings suggest that the cytotoxic effect of DT is associated with mitochondrial dysfunction-dependent apoptosis which is mediated through oxidative stress. Therefore, DT represents an interesting reference point for the development of new cytotoxic agent targeting IKK/NFκB pathway.