ABSTRACT
In this study, the effect of cordycepin (3’-deoxyadenosine), a major component of Cordyceps militaris, an ingredient of traditional Chinese medicine was investigated for the first time on apoptotsis in human neuroblastoma SK-N-BE(2)-C and melanoma SK-MEL-2 cells. Cordycepin significantly inhibited the proliferation of human neuroblastoma SK-N-BE(2)-C and human melanoma SK-MEL-2 cells with IC50 values of 120 mM and 80 mM, respectively. Cordycepin treatment at 120 mM and 80 mM, respectively, induced apoptosis in both cells and caused the increase of cell accumulation in a time-dependent manner at the apoptotic sub-G1 phase, as evidenced by the flow cytometry (FCM) and annexin V-fluorescein isothiocyanate (FITC) analyses. Western blot analysis revealed the induction of active caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage by cordycepin treatment. These results suggest that cordycepin is a potential candidate for cancer therapy of neuroblastoma and melanoma.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Deoxyadenosines/pharmacology , Humans , Melanoma/pathology , Neuroblastoma/pathologyABSTRACT
Cordycepin (3'-deoxyadenosine) has been shown to exhibit many pharmacological activities, including anti-cancer, anti-inflammatory, and anti-infection activities. However, the anti-skin photoaging effects of cordycepin have not yet been reported. In the present study, we investigated the inhibitory effects of cordycepin on matrix metalloproteinase-1 (MMP-1) and -3 expressions of the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed cordycepin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated NF-kappa B activity, which was determined by I kappa B alpha degradation, nuclear localization of p50 and p65 subunit, and NF-kappa B binding activity. However, UVB-induced NF-kappa B activation and MMP expression were completely blocked by cordycepin pretreatment. These findings suggest that cordycepin could prevent UVB-induced MMPs expressions through inhibition of NF-kappa B activation. In conclusion, cordycepin might be used as a potential agent for the prevention and treatment of skin photoaging.
Subject(s)
Humans , Infant, Newborn , Male , Aging/physiology , Cells, Cultured , Deoxyadenosines/pharmacology , Dermis/cytology , Dose-Response Relationship, Drug , Enzyme Induction/drug effects , Fibroblasts/drug effects , Gene Expression Regulation, Enzymologic , Matrix Metalloproteinase 1/antagonists & inhibitors , Matrix Metalloproteinase 3/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Skin/physiopathology , Ultraviolet RaysABSTRACT
OBJECTIVE: To compare the percentage of sperm tail membrane swelling under hypo-osmotic conditions between sperm treated with pentoxifylline and 2-deoxyadenosine. DESIGN: Experimental in vitro study. MATERIAL AND METHOD: Thirty normal semen samples from male partners of infertile couples were collected. After sperm preparation by two-layer Percoll gradient method, each sperm sample was divided into three specimens. Pentoxifylline and 2-deoxyadenosine were separately added into two specimens, while the third specimen was used as a control. Hypo-osmotic swelling test was performed in all specimens. Percentage of swollen spermatozoa in each specimen was evaluated. RESULTS: The mean percentage of swollen spermatozoa in the semen samples supplemented with pentoxifylline and 2-deoxyadenosine were both significantly higher than those in the control (82.8 +/- 7.7 and 83.0 +/- 9.5 vs 70.8 +/- 12.7; p < 0.001). There was no significant differences of swollen spermatozoa between pentoxifylline and 2-deoxyadenosine (p = 0.898). CONCLUSION: Addition of pentoxifylline and 2-deoxyadenosine to the sperm prepared by the two-layer Percoll gradient method can almost equally enhance the sperm membrane integrity. Therefore, it may be beneficial to add these compounds to sperm preparation for use in assisted reproduction.
Subject(s)
Deoxyadenosines/pharmacology , Enzyme Inhibitors/pharmacology , Humans , Infertility, Male , Male , Mutagens/pharmacology , Pentoxifylline/pharmacology , Reproductive Techniques, Assisted , Spermatozoa/drug effectsABSTRACT
There was a linear increase in poly (A+) polymerase activity in the C. arietinum epicotyls during germination. Six-day-old auxin treated seedlings showed about 3-4 fold stimulation in enzyme activity, accompanied with 3- fold rise in the relative abundance of poly (A+) RNA levels. Actinomycin D, cycloheximide, cordycepin and amino acid analogues caused dramatic decline in poly (A+) polymerase as well as poly (A+) RNA levels. It seems that auxin induced a de novo synthesis of this enzyme.
Subject(s)
Amino Acids/metabolism , Antineoplastic Agents/pharmacology , Cicer/drug effects , Cycloheximide/pharmacology , Dactinomycin/pharmacology , Deoxyadenosines/pharmacology , Electrophoresis, Polyacrylamide Gel , Gene Expression Regulation, Plant , Germination , Indoleacetic Acids/pharmacology , Poly A/metabolism , Polynucleotide Adenylyltransferase/isolation & purification , Protein Synthesis Inhibitors/pharmacology , RNA/metabolism , Seeds/drug effectsABSTRACT
Effect of pulse treatments of cordycepin, an analog of adenosine, on S and G2 phases of the cell cycle of the mitotically synchronous plasmodia of Physarum polycephalum has been studied. Various concentrations of the drug (50-200 micrograms ml-1) were found to be effective in delaying mitosis by several hours in both the phases. However, there was a significant increase in mitotic delay in those treated during G2. It is suggested that this extra delay during G2 could be due to the transcriptive level inhibition of specific RNA types, such as that of tubulins, whose gene activity is cell cycle regulated and turned on during G2 in Physarum, or alternatively because of a deficiency for ATP and the consequent inhibition of events such as mitotic spindle assembly and phosphorylation of histones.