In-depth analysis of metabolomics diversity of marine species through advanced mass spectrometric analysis is one of the most promising new tools for the development of marine drugs against mild and life-threatening diseases. Neurofibromas are a common type of tumor in the peripheral nervous system. Currently, there are very limited treatment options for neurofibromas. In our course of exploring potential therapeutic agents for neurofibroma treatment, the multi-informative molecular networking (MIMN) approach was proposed. The MIMNs of the Lendenfeldia sp. sponge extract and sub-fractions were established according to their inhibitory activity against several inflammatory chemokines (CCL3, CCL4, CCL5, CXCL1, CXCL8, and CXCL10) in neurofibroma cell line hTERT-NF1-ipNF95.11b-C (CRL-3390). The visualized MIMN revealed the anti-inflammatory potential of scalarane-enriched fractions, and the follow-up annotation and isolation led to the identification of a scalarane, 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (2). Our results revealed that the most abundant scalarane (2) dominated the anti-chemokine effect of Lendenfeldia sp. extract together with other scalaranes, indicating the potential application of sponge-derived scalaranes to be developed as therapeutic agents for neurofibromas.
A recent study of the EtOAc extract of the gorgonian Briareum excavatum afforded six new diterpenes of the briarane skeleton, excavatolides U-Z (1-6). The structures and relative stereochemistry of metabolites 1-6 were assigned on the basis of NMR studies and chemical methods. The structure, including the relative configuration of excavatolide U (1), was further confirmed by a single-crystal X-ray analysis. Some of the excavatolides have displayed significant cytotoxicity toward P-388 and HT-29 tumor cells.
Oral cancer is a malignant neoplasia that is more common in Asian than other regions, and men are at higher risk than women. Currently, clinical treatment for oral cancer consists of radiation therapy combined with chemotherapy. Therefore, it is important to find a drug that can inhibit the growth of cancer cells more effectively and safely. In this study, we examined the cytotoxicity of 4-carbomethoxyl-10-epigyrosanoldie E extracted from cultured soft coral Sinularia sandensis towards oral cancer cells. MTT cell proliferation and colony formation assays were used to evaluate cell survival, and immunofluorescence staining and Western blotting were employed to analyze the effects of 4-carbomethoxyl-10-epigyrosanoldie E on apoptosis and autophagy. 4-Carbomethoxyl-10-epigyrosanoldie E treatment also induced the formation of reactive oxygen species (ROS), which are associated with 4-carbomethoxyl-10-epigyrosanoldie E-induced cell death. In addition, the 4-carbomethoxyl-10-epigyrosanoldie E-induced antiproliferation effects on Ca9-22 and Cal-27 cells were associated with the release of cytochrome c from mitochondria, activation of proapoptotic proteins (such as caspase-3/-9, Bax, and Bad), and inhibition of antiapoptotic proteins (Bcl-2, Bcl-xl, and Mcl-1). 4-Carbomethoxyl-10-epigyrosanoldie E treatment also triggered endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/ATF4/CHOP apoptotic pathway. Moreover, increased expressions of Beclin-1, Atg3, Atg5, Atg7, Atg12, Atg 16, LC3-I, and LC3-II proteins indicated that 4-carbomethoxyl-10-epigyrosanoldie E triggered autophagy in oral cancer cells. In conclusion, our findings demonstrated that 4-carbomethoxyl-10-epigyrosanoldie E suppressed human oral cancer cell proliferation and should be further investigated with regard to its potential use as a chemotherapy drug for the treatment of human oral cancer.
One new 5alpha,8alpha-epidioxysterol, 3-acetylaxinysterol (1), along with one known sterol, axinysterol (2), were isolated from a Formosan sponge, Axinyssa sp.. The structures of the compounds were determined by spectroscopic methods and the absolute configuration of 2 was further confirmed by single-crystal X-ray diffraction analysis for the first time. Compound 2 exhibited significant cytotoxicity against K562 and Molt 4 cancer cell lines.
Angiogenesis and invasion are highly related with tumor metastatic potential and recurrence prediction in the most aggressive brain cancer, glioblastoma multiforme (GBM). For the first time, this study reveals that marine-sponge-derived stellettin B reduces angiogenesis and invasion. We discovered that stellettin B reduces migration of glioblastoma cells by scratch wound healing assay and invasion via chamber transwell assay. Further, stellettin B downregulates Akt/Mammalian Target of Rapamycin (Akt/mTOR) and Signal transducer and activator of transcription 3 (Stat3) signaling pathways, which are essential for invasion and angiogenesis in glioblastoma. This study further demonstrates that stellettin B affects filamentous actin (F-actin) rearrangement by decreasing the cross-linkage of phosphor-Girdin (p-Girdin), which attenuates glioblastoma cell invasion. Moreover, stellettin B blocks the expression and secretion of a major proangiogenic factor, vascular endothelial growth factor (VEGF), in glioblastoma cells. Stellettin B also reduces angiogenic tubule formation in human umbilical vein endothelial cells (HUVECs). In vivo, we observed that stellettin B decreased blood vesicle formation in developmental zebrafish and suppressed angiogenesis in Matrigel plug transplant assay in mice. Decreased VEGF transcriptional expression was also found in stellettin B–treated zebrafish embryos. Overall, we conclude that stellettin B might be a potential antiangiogenic and anti-invasion agent for future development of therapeutic agents for cancer therapy.
Urothelial carcinoma (UC) is the most common type of genitourinary cancer with high incidence and mortality rates in men. In this study, we used the BFTC-905 and T24 bladder cancer cell lines as in vitro models to investigate the pathways involved in flaccidoxide-induced apoptosis.We utilized MTT assays, colony assays, wound-healing assays and fluorescence with TUNEL to confirm the cytotoxicity of flaccidoxide in bladder cancer cell lines. Potential proliferative and apoptotic molecular mechanisms were evaluated by western blotting.The expression of anti-apoptotic proteins Bcl-2 and phosphorylated Bad (p-Bad) was attenuated with an increasing flaccidoxide concentration, while the expression of proapoptotic proteins Bax, Bad, cleaved caspase-3, cleaved caspase-9 and cleaved PARP-1 was found increased. Additionally, phosphorylation of phosphoinositide 3-kinases (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in the PI3K/AKT/mTOR pathway was reduced, leading to a reduction in the phosphorylation of downstream 70-kDa ribosomal protein S6 kinase 1 (p70S6K), S6 ribosomal protein (S6) and eukaryotic translation initiation factor 4B (eIF4B). However, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) protein phosphorylation was increased due to attenuation of the upstream phosphorylation of mTOR protein.Flaccidoxide-induced apoptosis in BFTC-905 and T24 cells is mediated by mitochondrial dysfunction and down-regulation the PI3K/AKT/mTOR/p70S6K signaling pathway.
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