ABSTRACT
This study investigated the mechanisms underlying the cytotoxicity of the green algae Ulva fasciata Delile. U. fasciata extract (UFE) inhibited the growth of HCT 116 human colon cancer cells by 50% at a concentration of 200 µg/ml. In addition, UFE stimulated the production of intracellular reactive oxygen species, an effect that was abolished by pretreatment with N-acetyl cysteine, which also inhibited the cytotoxic effects of UFE. UFE also induced morphological changes indicative of apoptosis, such as the formation of apoptotic bodies, DNA fragmentation, an increase in the population of apoptotic sub-G(1) phase cells, and mitochondrial membrane depolarization. Concomitant activation of the mitochondria-dependent apoptotic pathway occurred via modulation of Bax and Bcl-2 expression, resulting in disruption of the mitochondrial membrane potential and activation of caspase-9 and caspase-3. This is the first report to demonstrate the cytotoxic effect of U. fasciata on human colon cancer cells and to provide a possible mechanism for this activity.
Subject(s)
Apoptosis/drug effects , Colonic Neoplasms/drug therapy , Plant Extracts/pharmacology , Ulva/chemistry , Acetylcysteine/pharmacology , DNA Fragmentation/drug effects , HCT116 Cells , Humans , Mitochondrial Membranes/drug effects , Plant Extracts/antagonists & inhibitors , Reactive Oxygen Species/metabolismABSTRACT
Six new germacranolides, zawadskinolides A-F (1-6), and a new eudesmane glucoside, chrysantiloboside (7) were isolated from the aerial parts of Dendranthema zawadskii var. latilobum, along with thirteen known constituents. Their structures were elucidated by means of spectroscopic evidence. Bioassay showed that flavonoids such as apigenin (9), (-)-eriodictyol (10) and nepetin (12), as well as the sesquiterpene lactone, zawadskinolide F (6), inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells with IC50 values of 66.15, 132.55, 35.44, and 91.32 µM, respectively.
Subject(s)
Chrysanthemum/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Animals , Cells, Cultured , Flavonoids/chemistry , Flavonoids/pharmacology , Inhibitory Concentration 50 , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Mice , Nitric Oxide/antagonists & inhibitors , Sesquiterpenes, Eudesmane/chemistry , Sesquiterpenes, Eudesmane/pharmacology , Sesquiterpenes, Germacrane/chemistry , Sesquiterpenes, Germacrane/pharmacology , Spectrum Analysis/methodsABSTRACT
The antibacterial activities of vulgarone B, a component of Artemisia iwayomogi essential oil, were evaluated against some antibiotic-susceptible and -resistant human pathogens. Moreover, the effects of combining antibiotics, such as oxacillin, with vulgarone B were determined in this study. Significant inhibitory activities of Artemisia oils against antibiotic-susceptible and -resistant bacteria were confirmed by broth microdilution methods. The effects of vulgarone B on bacterial morphology and DNA were observed by scanning electron microscope and electrophoresis, respectively. In checkerboard microtiter tests, vulgarone B and A. iwayomogi oil combined with oxacillin resulted in synergism, or additive effects. Moreover, the safety of Artemisia oil and vulgarone B were confirmed in vivo. Both vulgarone B and the essential oil fraction of A. iwayomogi showed significant inhibitory activities against strains of antibioticsusceptible and -resistant bacteria. The oils showed synergism or additive effects when combined with oxacillin against two strains of Staphylococcus aureus. The antibiotic mechanism involved might be related to DNA cleavage. Thus, vulgarone B and the essential oil fraction of A. iwayomogi may be promising candidates for a safe, effective, natural agent active against antibiotic-resistant S. aureus, especially when combined with oxacillin.