[New and clinically used oncomarkers of bladder cancer]. / Nové a klinicky vyuzívané onkomarkery karcinómu mocového mechúra.

Bladder cancer is the fourth most common cancer in men and the eighth most common cancer in women. Oncomarkers play a crucial role in early detection of bladder cancer, as well as in treatment response monitoring and prognosis. Search for a new marker by molecular analysis is in progress because any diagnostic sensitivity and specificity enhancement is a great benefit for clinical practice.

Anti-proliferative and anti-angiogenic effects of CB2R agonist (JWH-133) in non-small lung cancer cells (A549) and human umbilical vein endothelial cells: an in vitro investigation.

Non-small cell lung cancer has one of the highest mortality rates among cancer-suffering patients. It is well known that the unwanted psychotropic effects of cannabinoids (CBs) are mediated via the CB(1) receptor (R), and selective targeting of the CB(2)R would thus avoid side effects in cancer treatment. Therefore, the aim of our study was to evaluate the effect of selective CB(2)R agonist, JWH-133, on A549 cells (non-small lung cancer) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay and DNA fragmentation assay were employed to evaluate the influence of JWH-133 (3-(1,1-dimethylbutyl)- 1-deoxy-Δ8-tetrahydrocannabinol) on investigated cancer cells. In addition, migration assay and gelatinase zymography were performed in HUVECs to asses JWH-133 anti-angiogenic activity. Our study showed that JWH-133 exerted cytotoxic effect only at the highest concentration used (10(-4) mol/l), while inhibition of colony formation was also detected at the non-toxic concentrations (10(-5)-10(-8) mol/l). JWH-133 was also found to be able to induce weak DNA fragmentation in A549 cells. Furthermore, JWH-133 at non-toxic concentrations inhibited some steps in the process of angiogenesis. It significantly inhibited endothelial cell migration after 17 h of incubation at concentrations of 10(-4)-10(-6) mol/l. In addition, JWH-133 inhibited MMP-2 secretion as assessed by gelatinase zymography. The present study demonstrates the in vitro anti-proliferative and anti-angiogenic potential of CB(2)R agonist, JWH-133, in nonsmall lung cancer cells and HUVECs. Our results generate a rationale for further in vivo efficacy studies with this compound in preclinical cancer models.

In vitro antiproliferative and antiangiogenic effects of Flavin7.

Flavin7 (F7) is a nutritional supplement often taken by cancer patients in Central Europe during chemo- and radiation therapy. In this study, investigation of the antiproliferative and antiangiogenic activities of this supplement were performed. Flavin7 showed antiproliferative activity in Jurkat as well as in HeLa cells. It significantly reduced the growth of both cancer cell lines at the doses of 200 microg/ml to 20 microg/ml (p<0.001 and p<0.01, respectively). In F7-treated Jurkat cells we found a significant increase in the fraction of cells with sub-G(0)/G(1) DNA content, which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V staining and DNA fragmentation. Furthermore, F7 at the doses of 100 microg/ml to 4 microg/ml inhibited endothelial cell migration and capillary tube formation what indicates its potential antiangiogenic properties. Flavin7 also inhibited the activity of matrix metalloproteinases (MMPs), preferentially MMP-9, at the doses of 100 microg/ml to 4 microg/ml. Our data suggest that F7 possesses marked antiproliferative and antiangiogenic properties in vitro. Further research is needed to elucidate also its in vivo activities.

Cruciferous phytoalexins: antiproliferative effects in T-Jurkat leukemic cells.

We tested antiproliferative activity of selected cruciferous phytoalexins including brassinin, 1-methoxybrassinin, (+/-)-spirobrassin, (+/-)-1-methoxyspirobrassinin and (+/-)-1-methoxyspirobrassinol, in leukemic Jurkat cell. The most effective of the tested phytoalexins was 1-methoxybrassinin with IC(50) 10 micromol l(-1). However, significant effect of all phytoalexines was also determined at concentration 1 micromol l(-1). In 1-methoxybrassinin-treated Jurkat cells, we found significant increase in the fraction of cells with a sub-G(0)/G(1) DNA content, which is considered to be a marker of cell death by apoptosis. Apoptosis was also confirmed by the annexin V staining. In summary, 1-methoxybrassinin exerted potent antiproliferative activity probably due to cell cycle arrest and apoptosis induction.

Antiproliferative and cancer chemopreventive activity of phytoalexins: focus on indole phytoalexins from crucifers.

Phytoalexins are produced by plants after exposure to physical, biological or chemical stress and a specific group of these metabolites represent indole phytoalexins produced by important plants of the family Cruciferae. With respect to the epidemiologically proven cancer chemopreventive properties of brassica vegetables, antiproliferative and anticarcinogenic activities of indole phytoalexins have been studied. Several indole phytoalexins (i.e. brassinin, spirobrassinin, brassilexin, camalexin, 1-methoxyspirobrassinin, 1-methoxyspirobrassinol and methoxyspirobrassinol methyl ether) have been found to possess significant antiproliferative activity against various cancer cells and this activity is supposed to be associated with the modulation of activity of transcription factors regulating cell cycle, differentiation and apoptosis. Indole phytoalexins (i.e. cyclobrassinin, spirobrassinin, brassinin) also exhibited cancer chemopreventive activity in models of mammary and skin carcinogenesis. Understanding the molecular and cellular mechanism of action of such drugs and their structure-activity relationships is necessary for development new derivatives with more favourable profile of antiproliferative and chemopreventive activities.