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1.
Smenospongine,a Sesquiterpene Aminoquinone from a Marine Sponge,Induces G1 Arrest or Apoptosis in Different Leukemia Cells
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Dexin Kong Shunji Aoki Yoshihiro Sowa Toshiyuki Sakai Motomasa Kobayashi 《Marine drugs》2008,6(3):480-488
Smenospongine, a sesquiterpene aminoquinone isolated from the marine sponge Dactylospongia elegans, was previously reported by us to induce erythroid differentiation and G1 phase arrest of K562 chronic myelogenous leukemia cells. In this study, we investigated the effect of smenospongine on the cell cycles of other leukemia cells, including HL60 human acute promyelocytic leukemia cells and U937 human histiocytic lymphoma cells by flow cytometric analysis. Smenospongine induced apoptosis dose-dependently in HL60 and U937 cells. The smenospongine treatment increased expression of p21 and inhibited phosphorylation of Rb in K562 cells, suggesting the p21-Rb pathway play an important role in G1 arrest in K562 cells. However, the p21 promoter was not activated by the smenospongine treatment based on a luciferase assay using the transfected K562 cells. Smenospongine might induce p21 expression via another mechanism than transactivation of p21 promoter. 相似文献
2.
Juan A. Rubiolo Eva Ternon Henar López-Alonso Olivier P. Thomas Félix V. Vega Mercedes R. Vieytes Luis M. Botana 《Marine drugs》2013,11(11):4419-4434
In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the cell cycle of this yeast. The compound induced cell cycle arrest in G2/M followed by an increase in cell DNA content and size. When the type of cell death was analyzed, we observed that crambescidin-816 induced apoptosis. The antifungal effect indicates that crambescidins, and mostly crambescidin-816, could serve as a lead compound to fight fungal infections. 相似文献
3.
Babak Esmaeelian Catherine A. Abbott Richard K. Le Leu Kirsten Benkendorff 《Marine drugs》2014,12(1):17-35
Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer. 相似文献
4.
Cancer cells grown in spheroid conditions interact with each other and the extracellular matrix, providing a better representation of the in vivo environment than two-dimensional cultures and are a more clinically relevant model. A discrete screening of genetically diverse marine samples in the spheroid assay led to the identification of a novel activity for the known compound furospinulosin 1. This compound shows activity against MDA-MB-231 triple negative breast cancer cells grown as spheroids and treated for 24 or 48 h. No cytotoxicity was seen in traditional two-dimensional adherent cultures treated for a longer time (72 h). A reverse phase protein array (RPPA) confirmed the limited activity of the compound in cells grown traditionally and revealed changes in protein expression when cells are grown as spheroids that are associated with better clinical prognosis. Analysis of the RPPA data through the Broad institute’s connectivity map suggested the hypothesis that furospinulosin 1 functions as an MEK inhibitor. Analysis of the RPPA data through STRING supports the apoptosis observed. The selectivity exhibited by furospinulosin 1 for triple negative breast cancer cells only when grown as spheroids makes it an interesting compound with strong therapeutic potential that merits further study. 相似文献
5.
Ming Liu Xiangzhong Zhao Jin Zhao Lin Xiao Haizhou Liu Cuicui Wang Linyou Cheng Ning Wu Xiukun Lin 《Marine drugs》2012,10(11):2596-2607
Mere15 is a novel polypeptide from Meretrix meretrix Linnaeus with cytotoxicity in solid cancer cells. In this study, we investigated its activity on human K562 chronic myelogenous leukemia cells. Mere15 inhibited the growth of K562 cells with IC50 values of 38.2 μg/mL. Mere15 also caused concentration dependent induction of apoptosis, with overproduction of reactive oxygen species and loss of mitochondrial membrane potential. Moreover, Mere15 arrested cell cycle progression at G0/G1 phase of K562 cells in a concentration dependent manner. In addition, Mere15 caused the disassembly of the microtubule cytoskeleton in K562 cells and inhibited the polymerization of tubulin in a cell free system via interaction with tubulin. We concluded that Mere15 was cytotoxic to K562 leukemia cells and the cytotoxicity was related to the apoptosis induction, cell cycle arrest and microtubule disassembly. These results implied that Merer15 was a broad spectrum anticancer polypeptide, not only cytotoxic to various solid cancer cells but also to the chronic myelogenous leukemia cells. Mere15 may have therapeutic potential for the treatment of leukemia. 相似文献