Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis

AbstractCordyceps sinensis, a fungus that parasitizes on the larva of Lepidoptera, has been used as a valued traditional Chinese medicine. We investigated the effects of water extracts of Cordyceps sinensis (WECS), and particularly focused on its anticancer and antimetastatic actions. Based on in vitro studies, we report that WECS showed an anticancer action, and this action was antagonized by an adenosine A3 receptor antagonist. Moreover, this anticancer action of WECS was promoted by an adenosine deaminase inhibitor. These results suggest that one of the components of WECS with an anticancer action might be an adenosine or its derivatives. Therefore, we focused on cordycepin (3′-deoxyadenosine) as one of the active ingredients of WECS. According to our experiments, cordycepin showed an anticancer effect through the stimulation of adenosine A3 receptor, followed by glycogen synthase kinase (GSK)-3β activation and cyclin D1 suppression. Cordycepin also showed an antimetastatic action through inhibiting platelet aggregation induced by cancer cells and suppressing the invasiveness of cancer cells via inhibiting the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and accelerating the secretion of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 from cancer cells. In conclusion, cordycepin, an active component of WECS, might be a candidate anticancer and antimetastatic agent

過酸化ベンゾイルの一般薬理学的研究

The pharmacological actions of benzoyl peroxide were investigated using the screening methods of general pharmacology. The results obtained in the present study were as follows: (1) In in vivo study, benzoyl peroxide did not exhibit analgesic, anti-convulsive, muscle-relaxant or hypnotic effects in mice. (2) Benzoyl peroxide did not affect the twitch response to electrical stimulation in isolated phrenic nerve-diaphragm preparation of rats. (3) Benzoyl peroxide did not affect the contractile response to acetylcholine in the isolated bronchus of rats, but significantly depressed the contractile responses to acetylcholine and Ba^ in isolated ileum of rats. (4) Benzoyl peroxide did not exhibit diuretic effects or hemolytic effects in rabbits. The in vivo results indicated that benzoyl peroxide has no effect on the central nervous system or the somatic nervous system of rats. However, at higher concentrations benzoyl peroxide depressed the contractile response of ileal smooth muscles. Therefore, our results suggest that excess benzoyl peroxide changes some physiological functions of smooth muscle tissue without changing the behavior or external appearance in vivo experiments

Age-related changes to vascular protease-activated receptor 2 in metabolic syndrome: A relationship between oxidative stress, receptor expression and endothelium-dependent vasodilation.

Protease-activated receptor 2 (PAR2) is expressed in vascular endothelium. Nitric oxide (NO)-cyclic GMP mediated vasodilation in response to 2-furoyl-LIGRLO-amide (2fLIGRLO), a PAR2-activating peptide, is impaired in aortas from aged SHRSP.Z-LeprThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Differential effects of mitogen-activated protein kinase pathway inhibitors on P-glycoprotein activation

The aim of this study was to evaluate the effects of the mitogen-activated protein kinase (MAPK) pathway inhibitors SB203580, CMPD-1, SB239063, SP600125, and FR180204 on the activity of P-glycoprotein (P-gp) and to assess whether the MAPK pathway affects P-gp directly. Changes in the fluorescence of residual rhodamine 123, a marker of P-gp activity, in the apical region of Caco-2 cells were measured in the presence of MAPK pathway inhibitors using time-lapse confocal laser scanning microscopy at 0, 10, 20, 30, and 60 min. Significant differences were observed between the fluorescence levels of control cells and cells treated with SB203580 for 20, 30, or 60 min. However, no significant change was observed in the residual rhodamine 123 fluorescence of cells treated with CMPD-1, SB239063, SP600125, or FR180204. Among the p38-MAPK pathway inhibitors investigated, CMPD-1 and SB239063 showed no detectable effect on the activity of P-gp. Further, JNK 1, 2, 3-MAPK pathway (SP600125) and ERK1/2 pathway (FR180204) inhibitors did not affect P-gp activity. However, SB203580 enhanced the transfer of rhodamine 123 across the apical cell membrane. Thus, SB203580 activated P-gp, although not through the p38-MAPK pathway. Importantly, the MAPK pathway did not affect P-gp activity shortly after treatment