Home About us Contact
|
Home About us Contact | ||
|
|
||
Various Cancer Cells (various + cancer_cell)
Terms modified by Various Cancer Cells Selected AbstractsRap1 and p38 MAPK mediate 8-chloro-cAMP-induced growth inhibition in mouse fibroblast DT cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006Young-Ho Ahn 8-Cl-cAMP, which is known to induce differentiation, growth inhibition, and apoptosis in various cancer cells, has been investigated as a putative anti-cancer drug. Previously, we reported that 8-Cl-cAMP and its metabolite 8-Cl-adenosine induce growth inhibition and apoptosis through p38 mitogen-activated protein kinase (MAPK) activation. To further investigate the signal mechanisms that regulate the cellular effects of 8-Cl-cAMP, we focused on a small GTPase Rap1 that is known to be involved in growth inhibition and reverse-transformation. 8-Cl-cAMP and 8-Cl-adenosine could increase Rap1 activity, which was blocked by ABT702,an adenosine kinase inhibitor. This suggests that 8-Cl-cAMP-induced Rap1 activation is also dependent on the metabolic degradation of 8-Cl-cAMP. Overexpression of a constitutively active mutant form of Rap1 (Rap1V12) attenuated cellular growth and soft-agar colony formation, which was basically the same effect as that observed with the 8-Cl-cAMP treatment. Furthermore, the Rap1V12 transfectant showed a high level of p38 MAPK activation. However, 8-Cl-cAMP-induced Rap1 activation was not diminished by SB203580, a p38 MAPK inhibitor, suggesting that Rap1 activation might act upstream of p38 MAPK activation during 8-Cl-cAMP-induced growth inhibition. J. Cell. Physiol. 209: 1039,1045, 2006. © 2006 Wiley-Liss, Inc. [source] Curcumin Suppresses the Paclitaxel-Induced Nuclear Factor-,B in Breast Cancer Cells and Potentiates the Growth Inhibitory Effect of Paclitaxel in a Breast Cancer Nude Mice ModelTHE BREAST JOURNAL, Issue 3 2009Hee Joon Kang MD Abstract:, Most anticancer agents activate nuclear factor kappa B (NF-,B), which can mediate cell survival, proliferation, and metastasis. Curcumin has been shown to inhibit the growth of various cancer cells, without toxicity to normal cells. The antitumor effects of curcumin could be due in part to the inactivation of NF-,B. We hypothesize that blocking NF-,B activity may augment paclitaxel cancer chemotherapy. In this study, we investigated whether the inactivation of NF-,B by curcumin would enhance the efficacy of paclitaxel for inhibiting breast cancer growth in vitro and in vivo. We confirmed that curcumin inhibited paclitaxel-induced activation of NF-,B and potentiated the growth inhibitory effect of paclitaxel in MDA-MB-231 breast cancer cells. The combination of curcumin with paclitaxel elicited significantly greater inhibition of cell growth and more apoptosis, compared with either agent alone. In an experimental breast cancer murine model using MDA-MB-231 cells, combination therapy with paclitaxel and curcumin significantly reduced tumor size and decreased tumor cell proliferation, increased apoptosis, and decreased the expression of matrix metalloprotease 9 compared with either agent alone. These results clearly suggest that a curcumin,paclitaxel combination could be a novel strategy for the treatment of breast cancer. [source] 1,,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093, profoundly inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2ANZ JOURNAL OF SURGERY, Issue 7 2001J. Akhter Background: 1,,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been shown to inhibit the proliferation of various cancer cells including colon, prostate, melanoma, osteosarcoma and breast cancer. Methods: The human hepatoma cell line (HepG2) was cultured with 1,25(OH)2D3 or one of two analogues EB1089 or CB1093 for various durations. Cellular proliferation was measured by uptake of [3H]thymidine, and cell numbers were determined by trypan blue exclusion counting. Results: 1,25(OH)2D3, EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90% after 5 days of treatment, compared to the untreated controls. Decreased proliferation was associated with an approximately 50% reduction in cell numbers at concentrations of up to 10,10 mol/L after 5 days of treatment with 1,25(OH)2D3. Cell proliferation rapidly recovered in cultures treated with lower concentrations of 1,25(OH)2D3 (10,10 and 10,11 mol/L) when 1,25(OH)2D3 was removed from the cultures by placing cells in serum containing medium without 1,25(OH)2D3. When HepG2 cells were treated with 10,8 mol/L 1,25(OH)2D3 for 5 weeks, there was still significant inhibition of proliferation, although at week 5 there was 66% inhibition compared to 93% at the end of week 1. Conclusions: 1,25(OH)2D3, EB1089 and CB1093 all significantly inhibit the proliferation of HepG2 hepatoblastoma cells, with EB1089 being the most potent at lower concentrations. Inhibition can be maintained for at least 4 weeks, but is reversed after removal of vitamin D3. [source] Rosiglitazone Inhibits Cell Proliferation by Inducing G1 Cell Cycle Arrest and Apoptosis in ADPKD Cyst-Lining Epithelia CellsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2010Yawei Liu Many drugs inhibiting cell proliferation have been proved to be effective in slowing the disease progression in ADPKD. Recent evidence has suggested that peroxisome proliferator-activated receptor , (PPAR,) ligands have anti-neoplasm effects through inhibiting cell growth and inducing cell apoptosis in various cancer cells. In the present study, we examined the expression of PPAR, in human ADPKD kidney tissues and cyst-lining epithelial cell line, and found that the expression of PPAR, was greater in ADPKD kidney tissues and cyst-lining epithelial cell line than in normal kidney tissues and human kidney cortex (HKC) cell line. Rosiglitazone inhibited significantly proliferation of cyst-lining epithelial cells in a concentration- and time-dependent manner. These effects were diminished by GW9662, a specific PPAR, antagonist. Cell cycle analysis showed a G0/G1 arrest in human ADPKD cyst-lining epithelial cells with rosiglitazone treatment. Analysis of cell cycle regulatory proteins revealed that rosiglitazone decreased the protein levels of proliferating cell nuclear antigen, pRb, cyclin D1, cyclin D2 and Cdk4 but increased the levels of p21 and p27 in a dose-dependent manner. Rosiglitazone also induced apoptosis in cyst-lining epithelial cells, which was correlated with increased bax expression and decreased bcl-2 expression. These results suggest PPAR, agonist might serve as a promising drug for the treatment of ADPKD. [source] Cantharidin induces apoptosis of human multiple myeloma cells via inhibition of the JAK/STAT pathwayCANCER SCIENCE, Issue 9 2008Morihiko Sagawa Multiple myeloma is an incurable B-cell malignancy requiring new therapeutic strategies in clinical settings. Interleukin (IL),6 signaling pathways play a critical role in the pathogenesis of multiple myeloma. The traditional Chinese medicine cantharidin (CTD) has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The aim of this study was to investigate the possibility of CTD as a novel therapeutic agent for the patients with multiple myeloma. We investigated the in vitro effects of CTD for its antimyeloma activity, and further examined the molecular mechanisms of CTD-induced apoptosis. CTD inhibited the cellular growth of human myeloma cell lines as well as freshly isolated myeloma cells in patients. Cultivation with CTD induced apoptosis of myeloma cells in a cell-cycle-independent manner. Treatment with CTD induced caspase-3, ,8, and ,9 activities, and it was completely blocked by each caspase inhibitor. We further examined the effect of CTD on the IL-6 signaling pathway in myeloma cells, and found that CTD inhibited phosphorylation of STAT3 at tyrosine 705 residue as early as 1 h after treatment and down-regulated the expression of the antiapoptotic bcl-xL protein. STAT3 directly bound and activated the transcription of bcl-xL gene promoter, resulting in the induction of the expression of bcl-xL in myeloma cells. The essential role of STAT3 in CTD effects was confirmed by transfection with the constitutively active and dominant negative form of STAT3 in U266 cells. In conclusion, we have demonstrated that CTD is a promising candidate to be a new therapeutic agent in signal transduction therapy. (Cancer Sci 2008; 99: 1820,1826) [source] Synthetic small interfering RNA targeting heat shock protein 105 induces apoptosis of various cancer cells both in vitro and in vivoCANCER SCIENCE, Issue 7 2006Seiji Hosaka We previously reported that heat shock protein 105 (HSP105), identified by serological analysis of a recombinant cDNA expression library (SEREX) using serum from a pancreatic cancer patient, was overexpressed in various human tumors and in the testis of adult men by immunohistochemical analysis. In the present study, to elucidate the biological function of the HSP105 protein in cancer cells, we first established NIH3T3 cells overexpressing murine HSP105 (NIH3T3-HSP105). The NIH3T3-HSP105 cells acquired resistance to apoptosis induced by heat shock or doxorubicin. The small interfering RNA (siRNA)-mediated suppression of HSP105 protein expression induced apoptosis in human cancer cells but not in fibroblasts. By a combination of siRNA introduction and doxorubicin or heat shock treatment, apoptosis was induced synergistically in a human colon cancer cell line, HCT116. In vivo, siRNA inoculation into the human gastric cancer cell line KATO-3 established in the flank of an NOD SCID mouse suppressed the tumor growth. This siRNA-induced apoptosis was mediated through caspases, but not the p53 tumor suppressor protein, even though the HSP105 protein was bound to wild-type p53 protein in HCT116 cells. These findings suggest that the constitutive overexpression of HSP105 in cancer cells is involved in malignant transformation by protecting tumor cells from apoptosis. HSP105 may thus be a novel target molecule for cancer therapy and a treatment regimen using synthetic siRNA to suppress the expression of HSP105 protein may provide a new strategy for cancer therapy. (Cancer Sci 2006; 97: 623,632) [source] Lasioglossins: Three Novel Antimicrobial Peptides from the Venom of the Eusocial Bee Lasioglossum laticeps (Hymenoptera: Halictidae)CHEMBIOCHEM, Issue 12 2009Václav, ovský Dr. Abstract Three novel structurally related pentadecapeptides, named lasioglossins, were isolated from the venom of the eusocial bee Lasioglossum laticeps. Their primary sequences were established as H-Val-Asn-Trp-Lys-Lys-Val-Leu-Gly-Lys-Ile-Ile-Lys-Val-Ala-Lys-NH2 (LL-I), H-Val-Asn-Trp-Lys-Lys-Ile-Leu-Gly-Lys-Ile-Ile-Lys-Val-Ala-Lys-NH2 (LL-II) and H-Val-Asn-Trp-Lys-Lys-Ile-Leu-Gly-Lys-Ile-Ile-Lys-Val-Val-Lys-NH2 (LL-III). These lasioglossins exhibited potent antimicrobial activity against both Gram-positive and Gram-negative bacteria, low haemolytic and mast cell degranulation activity, and a potency to kill various cancer cells in vitro. The lasioglossin CD spectra were measured in the presence of trifluoroethanol and sodium dodecyl sulfate solution and indicated a high degree of ,-helical conformation. NMR spectroscopy, which was carried out in trifluoroethanol/water confirmed a curved ,-helical conformation with a concave hydrophobic and convex hydrophilic side. To understand the role of this bend on biological activity, we studied lasioglossin analogues in which the Gly in the centre of the molecule was replaced by other amino acid residues (Ala, Lys, Pro). The importance of the N-terminal part of the molecule to the antimicrobial activity was revealed through truncation of five residues from both the N and C termini of the LL-III peptide. C-terminal deamidation of LL-III resulted in a drop in antimicrobial activity, but esterification of the C terminus had no effect. Molecular modelling of LL-III and the observed NOE contacts indicated the possible formation of a bifurcated H-bond between hydrogen from the Lys15 CONH peptide bond and one H of the C-terminal CONH2 to the Ile11 oxygen atom. Such interactions cannot form with C-terminal esterification. [source] | ||||||||||