1,721,036 research outputs found
Macromolecular organization and functional architecture of basement membranes
No full textBasement membranes (BMs) are extracellular laminar matrices produced by endothelial and epithelial cells. They are composed by three major intrinsic macromolecules: type IV collagen, laminin and heparan sulfate proteoglycan (HSP), and by two major extrinsic ones: fibronectin and type V collagen. The intrinsic components are assembled in a three-dimensional network (type IV collagen) to which cells stick (by laminin) and through which (HSP) they interact with the stromal compartment. The BM is a barrier to be crossed by any cell that leaves the stroma to enter into the circulation or vice versa. Metastatic tumor cells secrete a protease which specifically degrades the BM collagen and some evidence suggests that the same enzyme is used also by normal monocytes
The renaissance of Hypericum perforatum: bio-medical research caches up with folk medicine.
No full textThe traditional use of Hypericum perforatum L. (St. John's wort, Clusiaceae) in Western medicine was well known even before the 1600s: St. John's extracts were used to relieve various types of nervous disease long before depression was recognized as a well described pathology. Today, random controlled trials clearly confirm the efficacy of this plant extract over placebo in the treatment of mild to moderately severe depression. Of the different classes of H. perforatum secondary metabolites, the prenylated acylphloroglucinol hyperforin has emerged as key player for anti-depressant activity. But as well as Hypericum's anti-depressant property, several other pharmacological actions have now been documented - examples include anti-bacterial, anti-proliferative and anti-inflammatory - many of which may be related to hyperforin. These findings add support to the effectiveness of St. John's wort as a folk remedy in common use for treating skin injuries, burns and neuralgias. This review gives a historical overview of the plant, including its medical uses, plus a look at the chemical structure of the most relevant phyto-constituents. This is followed by a close analysis of recent data regarding the biological effects of hyperforin, focusing on anti-inflammatory and anti-tumor activities. The compound's clear and proven actions qualify it as an interesting lead candidate for countering inflammatory disease and cancer
Tetrahydrocurcumin inhibits HT1080 cell migration and invasion via the down regulation of MMPs and uPA.
No full textAIM:
Tetrahydrocurcumin (THC) is an active metabolite of curcumin. It has been reported to have similar pharmacological activity to curcumin. The proteases that participate in extracellular matrix (ECM) degradation are involved in cancer cell metastasis. The present study investigates the effect of an ultimate metabolite of curcumin, THC, on the invasion and motility of highly-metastatic HT1080 human fibrosarcoma cells.
METHODS:
The effect of THC on HT1080 cell invasion and migration was determined using Boyden chamber assay. Cell-adhesion assay was used for examining the binding of cells to ECM molecules. Zymography assay was used to analyze the effect of THC on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion from HT1080 cells. Tissue inhibitor of metalloproteinase (TIMP)-2 and membrane-type 1 matrix metalloproteinase (MT1-MMP) proteins levels were analyzed by Western blotting.
RESULTS:
Treatment with THC reduced HT1080 cell invasion and migration in a dose-dependent manner. THC also decreased the cell adhesion to Matrigel and laminin-coated plates. Analysis by zymography demonstrated that treatment with THC reduced the levels of MMP-2, MMP-9, and uPA. THC also inhibited the levels of MT1-MMP and TIMP-2 proteins detected by Western blot analysis.
CONCLUSION:
Our findings revealed that THC reduced HT1080 cell invasion and migration. The inhibition of cancer cell invasion is associated with the downregulation of ECM degradation enzymes and the inhibition of cell adhesion to ECM proteins
HIV-1 modulates the expression of gelatinase A and B in monocytic cells.
No full textThe levels of mRNA of both gelatinases A and B were dramatically decreased in HIV-infected cells, when compared to uninfected cells. The expression of gelatinase A in HIV-infected cells was selectively increased by tumor necrosis factor (TNFα) while the expression of gelatinase B was not affected. In contrast, in uninfected cells TNFα down regulated gelatinase B mRNA level, without affecting the gelatinase A. N-acethylcysteine (NAC) increased the levels of mRNA of both gelatinases. The conditioned media from HIV-infected and uninfected cells had comparable level of secreted gelatinase A protein. These data suggest that in monocytic cells different regulatory pathways control gelatinases A and B and that HIV could modulate in vivo the expression of these proteolytic enzymes, critically involved in regulation of invasion of basement membrane. © 1994 Academic Press, Inc
New phytoweapons to curb leukocyte elastase
No full textThis review does not presume to be exhaustive in the field of leukocyte elastase inhibitors. Instead, a general picture will be sketched to give the reader a brief update and encourage advances in this continuously growing sector of pharmacology, drug discovery and drug design. Three compounds with which the authors have direct experimental experience will be considered in detail as examples of newly emerging therapeutics from the ever-generous plant kingdo
Preliminary evaluation of inhibition of matrix-metalloprotease MMP-2 and MMP-9 by Passiflora edulis and P. foetida aqueous extracts
No full textCNTF up-regulation of TIMP-2 in neuroblastoma cells
No full textThe ciliary neurotrophic factor (CNTF) can regulate survival and differentiation of many types of developing and adult neurons; in metastatic SK-N-BE neuroblastoma cells, it promotes differentiation and neurite outgrowth. The expression of Gelatinase A (MMP-2) and its specific tissue inhibitor (TIMP-2), a degradative system whose balance is involved in matrix invasion and metastasis, was investigated in SK-N-BE cells cultured with and without CNTF or NGF. Zymographic analysis of conditioned media revealed that the cells constitutively secrete two gelatinases, mainly pro-MMP-2 but also traces of pro-MMP-9. In a time-course experiment in the presence of 25 ng/ml of CNTF, the MMP-2 mRNA expression showed no significant modulation, while TIMP-2 mRNA up-regulated to > 2-fold after 48 h and then fell dramatically. At the same concentrations, NGF showed no effect. TIMP-2 mRNA expression showed a dose-dependent increase of up to 8-fold from 1 to 250 ng/ml of CNTF and increased secretion of TIMP-2 was confirmed by Western blotting. MMP-2 was only slightly over-expressed under the same conditions, at either mRNA or protein level, with no correlation with neurocytokine concentration. These results suggest that boosting the expression of TIMP-2 by CNTF could restrain both matrix degradation following nervous system injury and neuroblastoma aggressivenes
Hormonal and basement membrane markers for immunoidentification of cultured human trophoblast cells.
No full textCurcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA.
No full textCurcumin (Cur), a component of turmeric (Curcuma longa), has been reported to exhibit antimetastatic activities, but the mechanisms remain unclear. Other curcuminoids present in turmeric, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) have not been investigated whether they exhibit antimetastatic activity to the same extent as curcumin. The regulation of matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) play important role in cancer cell invasion by cleavage of extracellular matrix (ECM). In this line, we comparatively examined the influence of Cur, DMC and BDMC on the expressions of uPA, MMP-2, MMP-9, membrane Type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-2), and in vitro invasiveness of human fibrosarcoma cells. The results indicate that the differential potency for inhibition of cancer cell invasion was BDMC> or =DMC>Cur, whereas the cell migration was not affected. Zymography analysis exhibited that curcumin, DMC and BDMC significantly decreased uPA, active-MMP-2 and MMP-9 but not pro-MMP-2 secretion from the cells in a dose-dependent manner, in which BDMC and DMC show higher potency than curcumin. The suppression of active MMP-2 level correlated with inhibition of MT1-MMP and TIMP-2 protein levels involved in pro-MMP-2 activation. Importantly, BDMC and DMC at 10 microM reduced MT1-MMP and TIMP-2 protein expression, but curcumin slightly reduced only MT1-MMP but not TIMP-2. In addition, three forms of curcuminoids significantly inhibited collagenase, MMP-2, and MMP-9 but not uPA activity. In summary, these data demonstrated that DMC and BDMC show higher antimetastasis potency than curcumin by the differentially down-regulation of ECM degradation enzymes
Modulation of proteolytic potential and differentiation by CNTF and BDNF in two mouse neuroblastoma clones: relation to invasion
No full textThe effect of CNTF and BDNF on a proteolytic complement instrumental to invasion and on differentiation was studied in two murine neuroblastoma clones, N1 and N7. At the membrane level, gelatinase MMP-2--mainly the activated form--was restrained by CNTF and BDNF to a residual 34% with both factors; membrane-type 1 MMP was down-regulated to 50% (10 h) and 34% (24 h) with both factors; and urokinase-type plasminogen activator was restrained mainly by BDNF to 70%. In the medium, the two gelatinases MMP-2 and MMP-9 were mainly in zymogen form: only MMP-2 was restrained in N1 cells, while only MMP-9 was restrained in N7 cells by both factors, single or in combination. These effects were paralleled by the induction of neurite outgrowth, which was more stimulated in the less differentiated clone. These dose-dependent and transient effects make CNTF and BDNF ideal candidates for constraining the potentially invasive behavior of nervous system tumor
- …
