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Human Cancer Cell Lines (human + cancer_cell_line)
Kinds of Human Cancer Cell Lines Selected AbstractsEffect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stromaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Takafumi Sangai Abstract Cancer-stromal interaction is well known to play important roles during cancer progression. Recently we have demonstrated that bone marrow-derived vascular endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10 kinds of human cancer cell line were implanted into the subctaneous tissue of the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG-1,/, ,-gal Tg or RAG-1,/, GFP Tg). The recruitment frequency of BMD-VE (%BMD-VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV), microvessel density (MVD) and stromal proportion (%St)] were measured. The correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0 to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD-VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the effect of tumor growth sites on the recruitment of the cells of interest, a human pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites: subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St = 9.7%, 9.1%, 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially up- or down-regulated in the cell line that induced an abundant stromal reaction. However they did not encoded the molecules that were directly involved in stromal cell recruitment (chemokines), differentiation (cytokines) or proliferation (growth factors). These results indicate that the recruitment of BMD-VE and -MF is required for stromal formation during cancer progression and that the cancer microenvironment is important in stromal reaction and the recruitment of BMD-VE and -MF. © 2005 Wiley-Liss, Inc. [source] Total Synthesis and Biological Assessment of Benzimidazole-Based Analogues of Epothilone A: Ambivalent Effects on Cancer Cell Growth InhibitionCHEMBIOCHEM, Issue 1 2006Fréderic Cachoux Dr. Benzimidazole-based analogues of cis - and trans -Epo A, 2 and 3, have been prepared through stereoselective total synthesis. Both compounds are highly potent antiproliferative agents, but the effects of side-chain replacement on cellular activity are ambivalent. While significantly enhanced potency is observed against a drug-sensitive human cancer cell line, 2 and 3 more susceptible to P-gp-mediated drug efflux than Epo A or trans -Epo A. [source] The histone deacetylase inhibitor MS-275 induces p21WAF1/Cip1 expression in human Hep3B hepatoma cellsDRUG DEVELOPMENT RESEARCH, Issue 2 2007Haiyuan Zhang Abstract MS-275 is a novel synthetic benzamide derivative histone deacetylase (HDAC) inhibitor, that has demonstrated antiproliferative activity in a variety of in vitro human cancer cell lines including breast, colon, lung, myeloma, ovary, pancreas, prostate, and leukemia. Currently, little information is available concerning the effects of MS-275 on liver cancer cells. In the current study, MS-275 was found to have potent actions against human hepatoma Hep3B cells including inhibition of cell proliferation and induction of apoptosis. MS-275 selectively up-regulated a cyclin-dependent kinase inhibitor, p21WAF1/Cip1 without alteration of p27WAF1. Expression of p21WAF1/Cip1 is considered to play a pivotal role in Hep3B cell growth arrest and induction of apoptosis. Induction of p21WAF1/Cip1 expression was accompanied by an accumulation of acetylated histones H3 and H4 associated specifically with p21WAF1/Cip1 gene. ChIP analysis revealed remarkable alterations in protein components bound to the promoter region of p21WAF1/Cip1 gene in response to MS-275 treatment. These included the degradation of HDAC1, HDAC3, and c-Myc, and as well as increased p300 and RNA polymerase II. The selective effect of MS-275 on the up-regulation of the p21WAF1/Cip1 gene whose expression was suppressed in the hepatoma cancer cell line indicated that it would be a very attractive approach in clinical liver cancer therapy. Drug Dev Res 68:61,70, 2007. © 2007 Wiley-Liss, Inc. [source] Down-regulation of heme oxygenase-2 is associated with the increased expression of heme oxygenase-1 in human cell linesFEBS JOURNAL, Issue 23 2006Yuanying Ding Intracellular heme concentrations are maintained in part by heme degradation, which is catalyzed by heme oxygenase. Heme oxygenase consists of two structurally related isozymes, HO-1 and HO-2. Recent studies have identified HO-2 as a potential oxygen sensor. To gain further insights into the regulatory role of HO-2 in heme homeostasis, we analyzed the expression profiles of HO-2 and the biochemical consequences of HO-2 knockdown with specific short interfering RNA (siRNA) in human cells. Both HO-2 mRNA and protein are expressed in the eight human cancer cell lines examined, and HO-1 expression is detectable in five of the cell lines, including HeLa cervical cancer and HepG2 hepatoma. Down-regulation of HO-2 expression with siRNA against HO-2 (siHO-2) caused induction of HO-1 expression at both mRNA and protein levels in HeLa and HepG2 cells. In contrast, knockdown of HO-1 expression did not noticeably influence HO-2 expression. HO-2 knockdown prolonged the half-life of HO-1 mRNA twofold in HeLa cells. Transient transfection assays in HeLa cells revealed that the 4.5-kb human HO-1 gene promoter was activated with selective knockdown of HO-2 in a sequence-dependent manner. Moreover, HO-2 knockdown caused heme accumulation in HeLa and HepG2 cells only when exposed to exogenous hemin. HO-2 knockdown may mimic a certain physiological change that is important in the maintenance of cellular heme homeostasis. These results suggest that HO-2 may down-regulate the expression of HO-1, thereby directing the co-ordinated expression of HO-1 and HO-2. [source] Identification of different isoforms of eEF1A in the nuclear fraction of human T-lymphoblastic cancer cell line specifically binding to aptameric cytotoxic GT oligomersFEBS JOURNAL, Issue 15 2003Barbara Dapas GT oligomers, showing a dose-dependent cytotoxic effect on a variety of human cancer cell lines, but not on normal human lymphocytes, recognize and form complexes with nuclear proteins. By working with human T-lymphoblastic CCRF-CEM cells and by using MS and SouthWestern blotting, we identified eukaryotic elongation factor 1 alpha (eEF1A) as the main nuclear protein that specifically recognizes these oligonucleotides. Western blotting and supershift assays confirmed the nature of this protein and its involvement in forming a cytotoxicity-related complex (CRC). On the contrary, normal human lymphocytes did not show nuclear proteins able to produce CRC in a SouthWestern blot. Comparative bidimensional PAGE and Western-blotting analysis for eEF1A revealed the presence of a specific cluster of spots, focusing at more basic pH, in nuclear extracts of cancer cells but absent in those of normal lymphocytes. Moreover, a bidimensional PAGE SouthWestern blot demonstrated that cytotoxic GT oligomers selectively recognized the more basic eEF1A isoform expressed only in cancer cells. These results suggest the involvement of eEF1A, associated with the nuclear-enriched fraction, in the growth and maintenance of tumour cells, possibly modulated by post-translational processing of the polypeptide chain. [source] Eight New Diterpenoids from the Roots of Euphorbia nematocyphaHELVETICA CHIMICA ACTA, Issue 11 2008Fei He Abstract From the dried roots of Euphorbia nematocypha, eight new diterpenoids, with ent -atisane (i.e., 1,5) and isopimarane (i.e., 6,8) type skeletons, together with five known compounds, were isolated. The structures of these new compounds were elucidated by spectroscopic data. Compounds 1,8 were evaluated for their cytotoxicity against a small panel of human cancer cell lines. [source] Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell linesINTERNATIONAL JOURNAL OF CANCER, Issue 1 2009Piyali Dasgupta Abstract Cigarette smoking is strongly correlated with the onset of nonsmall cell lung cancer (NSCLC). Nicotine, an active component of cigarettes, has been found to induce proliferation of lung cancer cell lines. In addition, nicotine can induce angiogenesis and confer resistance to apoptosis. All these events are mediated through the nicotinic acetylcholine receptors (nAChRs) on lung cancer cells. In this study, we demonstrate that nicotine can promote anchorage-independent growth in NSCLCs. In addition, nicotine also induces morphological changes characteristic of a migratory, invasive phenotype in NSCLCs on collagen gel. These morphological changes were similar to those induced by the promigratory growth factor VEGF. The proinvasive effects of nicotine were mediated by ,7-nAChRs on NSCLCs. RT-PCR analysis showed that the ,7-nAChRs were also expressed on human breast cancer and pancreatic cancer cell lines. Nicotine was found to promote proliferation and invasion in human breast cancer. The proinvasive effects of nicotine were mediated via a nAChR, Src and calcium-dependent signaling pathway in breast cancer cells. In a similar fashion, nicotine could also induce proliferation and invasion of Aspc1 pancreatic cancer cells. Most importantly, nicotine could induce changes in gene expression consistent with epithelial to mesenchymal transition (EMT), characterized by reduction of epithelial markers like E-cadherin expression, ZO-1 staining and concomitant increase in levels of mesenchymal proteins like vimentin and fibronectin in human breast and lung cancer cells. Therefore, it is probable that the ability of nicotine to induce invasion and EMT may contribute to the progression of breast and lung cancers. © 2008 Wiley-Liss, Inc. [source] Lack of functional erythropoietin receptors of cancer cell linesINTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Magdalena Laugsch Abstract Erythropoietin (Epo) therapy reduces red cell transfusion requirements and improves the quality of life of anemic cancer patients receiving chemotherapy. However, there is concern that Epo may promote tumor growth. We investigated by real-time RT-PCR, immunofluorescence microscopy, Western blotting and cell growth analysis whether human cancer cell lines (SH-SY5Y, MCF7, HepG2, U2-OS, HeLa, HEK293T, RCC4, HCT116, 7860wt and SW480) possess functional Epo receptors (EpoR). We detected EpoR mRNA in all cell lines. Neither hypoxia nor Epo treatment altered the level of EpoR mRNA expression. Four commonly used commercial antibodies proved to be unsuitable for immunoblot procedures because they cross-reacted with several proteins unrelated with EpoR. Depending on the antibody used, EpoR was localized to the plasma membrane, the cytoplasm or the nucleus. Experiments with small interfering RNA showed that EpoR protein was not expressed by the tumor cells except by UT7/Epo leukemia cells, which served as an EpoR positive control line, and by cells transfected with the human EpoR gene. Apart from UT7/Epo, none of the tumor cell lines responded to Epo treatment with phosphorylation of signaling molecules or with cell proliferation. © 2007 Wiley-Liss, Inc. [source] Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1, (HIF-1,) through inhibiting protein synthesisJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Dae-Hee Lee Abstract Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1, (HIF-1,) in normoxia. In this study, under hypoxic conditions (1% O2), we examined the effect of quercetin on the intracellular level of HIF-1, and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1, accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1, accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O2) in the presence of 100 µM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1, accumulation were observed under hypoxic conditions. Treatment with 100 µM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1, accumulation during hypoxia. These results suggest that suppression of HIF-1, accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. J. Cell. Biochem. 105: 546,553, 2008. © 2008 Wiley-Liss, Inc. [source] STAT proteins: From normal control of cellular events to tumorigenesis,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2003Valentina Calņ Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is made up of STAT2, STAT4, and STAT6, which are activated by a small number of cytokines and play a distinct role in the development of T-cells and in IFN, signaling. The other group includes STAT1, STAT3, and STAT5, activated in different tissues by means of a series of ligands and involved in IFN signaling, development of the mammary gland, response to GH, and embriogenesis. This latter group of STATS plays an important role in controlling cell-cycle progression and apoptosis and thus contributes to oncogenesis. Although an increased expression of STAT1 has been observed in many human neoplasias, this molecule can be considered a potential tumor suppressor, since it plays an important role in growth arrest and in promoting apoptosis. On the other hand, STAT3 and 5 are considered as oncogenes, since they bring about the activation of cyclin D1, c-Myc, and bcl-xl expression, and are involved in promoting cell-cycle progression, cellular transformation, and in preventing apoptosis. J. Cell. Physiol. 197: 157,168, 2003© 2003 Wiley-Liss, Inc. [source] Novel quinolone CHM-1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell lineJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2009Shu-Chun Hsu Abstract Novel 2-phenyl-4-quinolone compounds have potent cytotoxic effects on different human cancer cell lines. In this study, we examined anticancer activity and mechanisms of 20-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone (CHM-1) in human osterogenic sarcoma U-2 OS cells. CHM-1-induced apoptosis was determined by flow cytometric analysis, DAPI staining, Comet assay, and caspase inhibitors. CHM-1-inhibited cell migration and invasion was assessed by a wound healing assay, gelatin zymography, and a Transwell assay. The mechanisms of CHM-1 effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM-1 induced G2/M arrest and apoptosis at an IC50 (3 µM) in U-2 OS cells and caspase-3, -8, and -9 were activated. Caspase inhibitors increased cell viability after exposure to CHM-1. CHM-1-induced apoptosis was associated with enhanced ROS generation, DNA damage, decreased ,,m levels, and promotion of mitochondrial cytochrome c release. CHM-1 stimulated mRNA expression of caspase-3, -8, and -9, AIF, and Endo G. In addition, CHM-1 inhibited cell metastasis at a low concentration (<3 µM). CHM-1 inhibited the cell metastasis through the inhibition of MMP-2, -7, and -9. CHM-1 also decreased the levels of MAPK signaling pathways before leading to the inhibition of MMPs. In summary, CHM-1 is a potent inducer of apoptosis, which plays a role in the anticancer activity of CHM-1. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1637,1644, 2009 [source] Novel selective cytotoxicity of wild sarsaparilla rhizome extractJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2006Y. G. Huang Among six fractions, including total extract and fractions of hexane, ethyl acetate, butanol, water and boiling water extracted and separated from wild sarsaparilla rhizome, the hexane fraction (HRW) was the most effective in eliminating four different human cancer cell lines with cellular viability less than 6.8%. HRW exhibited the highest potency against human leukaemia cells with an IC50 (concentration that inhibited the growth rate of cells by 50%) of 3.3 ± 0.3 ,g mL,1, which was 17.6-fold smaller than that against normal human umbilical vein endothelial cells (IC50, 58.0 ± 1.5 ,g mL,1). For its rich natural resources, simple extraction procedure and high yield (3.2%), HRW has the potential to be developed as a selective anti-cancer nutraceutical or pharmaceutical natural health product with low side effects and high economical return. [source] Cytotoxic activity and effect on nitric oxide production of tirucallane-type triterpenesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2005Ibeth Oviedo Chįvez Hexane extract from the bark of Amphipterygium adstringens, as well as its principal constituents, masticadienonic acid (1) and 3,-hydroxymasticadienolic acid (2), inhibited the growth of five human cancer cell lines. Derivatives of 1, namely 24,25S -dihydromasticadienonic acid (3) and masticadienolic acid (4), were also evaluated. The results showed that both 3 and 4 had greater activity than 1 on colon cancer cell lines. The effects of 1,4 on the production of nitric oxide (NO) from both resting and lipopolysaccharide-activated macrophages were determined. It was found that 1, 2 and 4 caused an increase in NO release from resting macrophages; in lipopolysaccharide-activated macrophages, only 2 and 4 caused an increase in NO production. [source] Encapsulation of naturally occurring flavonoids into liposomes: physicochemical properties and biological activity against human cancer cell linesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2004M. Goniotaki Liposomes consisting of egg phosphatidylcholine were prepared by a thin-film hydration method followed by sonication and were used to investigate the percentage encapsulation of four flavonoids (quercetin, rutin, isoscutellarein and isoscutellarein diglycoside). The lipid recovery and the flavonoid-to-lipid molar ratio were measured using high-performance thin-layer chromatography/flame ionization detection and UV-vis spectroscopy. Differential scanning calorimetry was used to study the effect of the flavonoids on the phase transition temperature and on the enthalpy of the main phase transition of dipalmitoylphosphatidylcholine bilayers, and their ability to influence the membrane fluidity. The final liposomal formulation incorporating flavonoids, as well as free flavonoids, were tested for their activity against human cancer cell lines using the sulforhodamine B assay. The results showed that the encapsulation efficiency varied from 95% (0.21 flavonoid-to-lipid molar ratio) to 37.5% (0.09 flavonoid-to-lipid molar ratio) for isoscutellarein and its glycoside, respectively. The differential scanning calorimetry data showed close thermal and dynamic effects depending on the structure of the flavonoids, and suggest that there is a relationship between flavonoid molecular structure and the interaction with model membranes. Liposomal isoscutellarein showed improved growth inhibiting activity against all cell lines tested in comparison with that of its free form, which was inactive (>100 ,M). [source] Melatonin modulates the expression of VEGF and HIF-1, induced by CoCl2 in cultured cancer cellsJOURNAL OF PINEAL RESEARCH, Issue 2 2008Min Dai Abstract:, Melatonin is an important natural oncostatic agent. At present there are no data available as to its possible influence on tumor angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. It is well known that vascular endothelial growth factor (VEGF) is crucial to a solid tumor's higher vascularization and development. To investigate the possible influence of melatonin on angiogenesis, we studied the effect of melatonin on endogenous VEGF expression in three human cancer cell lines (PANC-1, HeLa and A549 cells). In this study, we report that physiologic concentrations of melatonin have no obvious impact on the VEGF expression, whereas pharmacologic concentrations of melatonin suppress the VEGF mRNA and protein levels induced by hypoxia mimetic cobalt chloride (CoCl2). Melatonin also decreases hypoxia-inducible factor (HIF)-1, protein levels, suggesting a role for transcription factor HIF-1 in the suppression of VEGF expression. The effect of pharmacologic concentrations of melatonin on VEGF and HIF-1, under normoxia is uncertain, which indicates that the regulatory mechanisms of VEGF in the absence or presence of CoCl2 are different and other or additional transcription factors may be involved. Taken together, our data show that melatonin in high concentrations markedly reduces the expression of endogenous VEGF and HIF-1, induced by CoCl2 in cultured cancer cells. [source] Combined BubR1 protein down-regulation and RASSF1A hypermethylation in Wilms tumors with diverse cytogenetic changesMOLECULAR CARCINOGENESIS, Issue 9 2008Masayuki Haruta Abstract BUB1B and RASSF1A genes play specific roles in the mitotic checkpoint, and their defects may cause chromosome instability or aneuploidy in mouse fibroblasts and human cancer cell lines; however, few studies have reported a correlation between defects in these genes and chromosome changes in human tumor samples. We examined chromosome abnormalities in 25 Wilms tumors by metaphase comparative genomic hybridization, and classified them into 14 hyperdiploid (50,,,chromosomes), 2 near-or-pseudodiploid, and 9 diploid tumors. We also examined various molecular aspects of BUB1B and RASSF1A, and evaluated the relationship between chromosome changes and the status of both genes. No tumors showed BUB1B mutation. BubR1 protein (BUB1B gene product) expression was undetectable or decreased in five of six hyperdiploid or near-or-pseudodiploid tumors and increased in four of five diploid tumors, whereas all seven tumors examined showed BUB1B mRNA expression irrespective of their chromosome pattern. Furthermore, while complete promoter methylation of RASSF1A was found in 13 of 16 hyperdiploid or near-or-pseudodiploid tumors, unmethylated RASSF1A was found in 5 of 9 diploid tumors. Partial RASSF1A methylation was found in three hyperdiploid or near-or-pseudodiploid tumors and in four diploid tumors. Thus, BubR1 protein expression decreased, and the promoter region of RASSF1A was completely methylated in the great majority of hyperdiploid or near-or-pseudodiploid tumors, BubR1 protein expression increased and RASSF1A was unmethylated in the majority of diploid tumors. These findings suggest that the combined BubR1 protein down-regulation and RASSF1A hypermethylation might be implicated in the formation of chromosomal changes found in Wilms tumors. © 2008 Wiley-Liss, Inc. [source] Metabolism of curcumin and induction of mitotic catastrophe in human cancer cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 9 2008Julia S. Dempe Abstract In cultured cells, curcumin (CUR) causes cell death by interfering with mitosis and leading to fragmented nuclei and disrupted microtubules, a process named mitotic catastrophe. In order to clarify the role of the known CUR metabolites hexahydro-CUR (HHC) and CUR-glucuronide (CUR-gluc) in mitotic catastrophe, the effects of CUR were studied in three human cancer cell lines with different metabolism of CUR. In Ishikawa and HepG2 cells, CUR was metabolized to HHC and small amounts of octahydro-CUR (OHC), whereas the only metabolism in HT29 cells was the formation of CUR-gluc. Despite their different metabolism, all three cell systems responded to CUR with arrest in G2/M phase and mitotic catastrophe. Fractionation of the cells showed that concentrations of CUR were higher in the ER and cytosol than in the incubation medium by a factor of up to about 150 and 8, respectively. In contrast to CUR, the metabolite HHC and the products of spontaneous degradation did not elicit any effects in Ishikawa cells. These results imply that the causative agent of mitotic catastrophe is the parent CUR molecule, whereas reductive metabolism and chemical degradation render CUR inactive. [source] Involvement of MAPK, Bcl-2 family, cytochrome c, and caspases in induction of apoptosis by 1,6- O,O -diacetylbritannilactone in human leukemia cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 2 2007Min-Hsiung Pan Abstract 1,6- O,O -diacetylbritannilactone (OODBL) isolated from Inula britannica, exhibits potent antitumor activity against several human cancer cell lines. However, the molecular mechanism of OODBL in the induction of anticancer activity is still unclear. In the present study, we demonstrated that OODBL induced the occurrence of apoptosis in human leukemic (HL-60) cells and cell arrest at the S phase. On the other hand, activation of caspase-8, -9, and -3, phosphorylation of Bcl-2 and Bid, and increased release of cytochrome c from mitochondria into cytosolic fraction were detected in OODBL-treated HL-60 cells. We further demonstrated that production of reactive oxygen species (ROS), activation of mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) signaling pathways may play an important role in OODBL-induced apoptosis. The results from the present study highlight the molecular mechanisms underlying OODBL-induced anticancer activity. [source] In vitro cytotoxic, antiprotozoal and antimicrobial activities of medicinal plants from VanuatuPHYTOTHERAPY RESEARCH, Issue 6 2010Gesine Bradacs Abstract Sixty-three extracts obtained from 18 plants traditionally used in the South Pacific archipelago Vanuatu for the treatment of infectious diseases were screened for antimicrobial and antiprotozoal activities. In addition, the extracts were subjected to a detailed analysis on cytotoxic effects toward a panel of human cancer cell lines, designed as a smaller version of the NCI60 screen. Intriguingly, 15 plant extracts exhibited strong cytotoxic effects specific for only one cancer cell line. Extracts of the leaves of Acalypha grandis Benth. significantly affected Plasmodium falciparum without showing obvious effects against the other protozoa tested. The leaves of Gyrocarpus americanus Jacq. displayed significant activity against Trypanosoma b. brucei and the leaves of Tabernaemontana pandacaqui Lam. I as well as the stems of Macropiper latifolium (L.f.) against Trypanosoma cruzi. In contrast none of the extracts showed relevant antibacterial or antifungal activity. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quercetin inhibited murine leukemia WEHI-3 cells in vivo and promoted immune responsePHYTOTHERAPY RESEARCH, Issue 2 2010Chun-Shu Yu Abstract Enhanced flavonoid consumption is closely related with a reduced cancer incidence as shown in epidemiological studies. Quercetin (3,5,7,3,,4,-pentahydroxylflavone) is one of the active components of flavonoids which exist in natural plants, particularly in onions and fruits. It was reported that quercetin induced apoptosis in human cancer cell lines, including human leukemia HL-60 cells, but there is no available information as to its effects on leukemia cells in vivo. The purpose of the present studies was to focus on the in vivo effects of quercetin on leukemia WEHI-3 cells. The effects of quercetin on WEHI-3 cells injected into BALB/c mice were examined. Quercetin decreased the percentage of Mac-3 and CD11b markers, suggesting that the differentiation of the precursors of macrophages and T cells was inhibited. There was no effect on CD3 levels but increased CD19 levels. Quercetin decreased the weight of the spleen and liver compared with the olive oil treated animals. Quercetin stimulated macrophage phagocytosis of cells isolated from peritoneum. Quercetin also promoted natural killer cell activity. Based on pathological examination, an effect of quercetin was observed in the spleen of mice previously injected with WEHI-3 cells. Apparently, quercetin affects WEHI-3 cells in vivo. Copyright © 2009 John Wiley & Sons, Ltd. [source] Antiproliferative activity of Hungarian Asteraceae species against human cancer cell lines.PHYTOTHERAPY RESEARCH, Issue 12 2007Part I Abstract Aqueous and organic extracts of 25 selected species from four tribes of Hungarian Asteraceae were screened in vitro for antiproliferative activity against HeLa (cervix epithelial adenocarcinoma), A431 (skin epidermoid carcinoma) and MCF7 (breast epithelial adenocarcinoma) cells, using the MTT assay. Twenty five of the 228 tested extracts from different parts of the species of Astereae (6), Inuleae (3), Heliantheae (5) and Anthemideae (11) demonstrated a substantial antiproliferative effect (at least 50% inhibition of cell proliferation) at 10 µg/mL against one or more of the cell lines. Complete dose-response curves were generated and IC50 values were calculated for these active extracts, and their direct cytotoxic effects were determined. In summary, 11 of the tested 25 plants were found to be active and 4 of them (Anthemis ruthenica, Erigeron canadensis, Erigeron annuus and Inula ensifolia) had not been studied previously for either active compounds or anticancer properties. Copyright © 2007 John Wiley & Sons, Ltd. [source] In vitro antiproliferative effect of six Salvia species on human tumor cell linesPHYTOTHERAPY RESEARCH, Issue 8 2006Giovina Fiore Abstract This study was designed to examine the in vitro antiproliferative activity of the methanol crude extracts of six Salvia species: Salvia dominica L. leaves, Salvia lanigera Desf. aerial parts, Salvia menthaefolia Ten. roots, Salvia palaestina Benth. aerial parts, Salvia sclarea L. roots and Salvia spinosa L. aerial parts. Extracts were screened for their possible antitumoral activity by MTT test on nine human cancer cell lines: glioblastoma (DBTRG-05MG, T98G, U-87MG), colorectal adenocarcinoma (WiDr and HT-29), prostate adenocarcinoma (MDA Pca2b), choriocarcinoma (JEG-3), endometrium adenocarcinoma (HEC-1A) and B lymphoblast (CIR). IC50 values were determined for only five extracts and ranged from 90 to 400 mg/mL approximately. Salvia menthaefolia extract exhibited marked antiproliferative activity against all tumor cell lines showing lower IC50 values, while S. spinosa, S. sclarea and S. dominica extracts showed a degree cytotoxic activity dependent on the cell line type. Finally S. palaestina extract revealed a moderate antiproliferative effect only against three cell lines. Salvia lanigera extract displayed toxic activity at all concentrations tested. The results strengthen the evidence that the genus Salvia could be considered a natural resource of potential antitumor agents. Copyright © 2006 John Wiley & Sons, Ltd. [source] In Vitro culture studies of FlorEssence® on human tumor cell linesPHYTOTHERAPY RESEARCH, Issue 2 2005Joseph Tai Abstract FlorEssence® (FE) is an herbal tea widely used by patients to treat chronic conditions in North America, particularly cancer patients during chemo- and radiation therapy. Although individual components of FE have antioxidant, antiestrogenic, immunostimulant and antitumor properties, in vitro evidence of anticancer activity for the herbal tea itself is still lacking. We studied the antiproliferative effect of FE on MCF7 and MDA-MB-468 human breast cancer, and Jurkat and K562 leukemia cell lines. We found that FE significantly inhibited the proliferation of both breast and leukemia cells in vitro only at high concentrations, with 50% inhibition of MDA-MB-468 cells at about 1[sol ]20 dilution, Jurkat cells at about 1[sol ]10 dilution and MCF7 and K562 cells at less than 1[sol ]10 dilution. Flow cytometry analysis showed that treatment with a high concentration of FE induced G2[sol ]M arrest in MCF7 and Jurkat cells, with also an increased SubG0[sol ]G1 fraction in MCF7 cells. MDA-MB-468 cells showed a significantly increased Sub G0[sol ]G1 fraction after treatment with 1[sol ]10 dilution of FE while the cell cycle of K562 was unaffected. When MCF7 and MDA-MB-468 breast cancer cells were treated with a combination of FE with either paclitaxel or cisplatin, results showed that only the combination of 1[sol ]20 dilution of FE with 0.5 µM cisplatin resulted in a small but significantly higher MCF7 cell survival than 0.5 µM cisplatin treatment alone. FE at 1[sol ]20 and 1[sol ]50 dilutions did not affect the antiproliferative properties of these two commonly used chemotherapeutic agents. The results suggest that FE at high concentrations show differential inhibitory effect on different human cancer cell lines. Further studies are needed to assess the biological activities of FE. Copyright © 2005 John Wiley & Sons, Ltd. [source] Antioxidant and cytotoxic activities of Hypericum sp. on brine shrimps and human cancer cell linesPHYTOTHERAPY RESEARCH, Issue 8 2002M. Couladis Abstract Ten different samples of five Hypericum sp. were tested on brine shrimps, human colon carcinoma and human hepatoma cell lines for their cytotoxic activities. H. triquetrifolium Turra. (Rafina) showed the highest activity (LC50,=,22,mg/mL) on brine shrimps, while the extracts of the other nine samples showed significant to moderate activities (LC50 from 37 to 107,mg/mL). H. empetrifolium Wild. (Parnon) showed the highest activity in human colon carcinoma and human hepatoma cell lines, with LC50 values 29 and 25.1,mg/mL, respectively, while the LC50 values of the other samples were more than 45,mg/mL. It is very interesting to observe that most Hypericum samples showed good antioxidant activity in vitro. Copyright © 2002 John Wiley & Sons, Ltd. [source] Marine cytotoxic macrolides haterumalides and biselides, and related natural productsTHE CHEMICAL RECORD, Issue 4 2007Hideo Kigoshi Abstract Marine animals and plants are rich sources of bioactive natural products. Haterumalides and biselides, isolated from Okinawan marine animals, are 14-membered macrolides with strong cytotoxicity against human cancer cell lines. This review highlights the isolation, structures, bioactivities, and total synthesis of haterumalides, biselides, and related natural products. © 2007 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 7: 254,264; 2007: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20119 [source] Expression of toll-like receptor-9 is increased in poorly differentiated prostate tumors,THE PROSTATE, Issue 8 2010Marja-Riitta Väisänen Abstract BACKGROUND Toll-like receptor-9 (TLR9) is a cellular receptor for bacterial and vertebrate DNA. In addition to cells of the immune system, it is also expressed in various human cancer cell lines, including prostate cancer. We demonstrated previously that synthetic TLR9 ligands induce matrix metalloproteinase-13-mediated invasion in TLR9-expressing prostate cancer cells in vitro. Other studies have suggested possible sex steroid regulation of the function of the various TLRs. The role of TLR9 in the pathophysiology of prostate or any cancer is, however, unknown. METHODS Expression of TLR9, androgen receptor (AR), or the estrogen receptors , (ER,) and , (ER,) were studied with immunohistochemistry in prostate cancer (n,=,62) and benign prostatic hyperplasia (n,=,45) specimens. TLR9 staining scores were compared with tumor stage, Gleason score, prostate-specific antigen (PSA) concentrations before tissue sampling and with the staining scores of AR, ER,, and ER,. RESULTS TLR9 expression was statistically significantly increased in prostate cancer epithelium and stroma, as compared with the same cellular compartments in benign hyperplasia. Significantly increased (P,=,0.04) TLR9 expression was detected in cancers with high Gleason score (>7, n,=,23), as compared with lower Gleason scores (,7, n,=,39). No statistically significant associations were detected between TLR9 expression scores and PSA concentrations or tumor staging. Prostate adenocarcinoma cells were all positive for TLR9, AR, and ER, but negative for ER, expression. In cancer stroma cells, increased TLR9 expression was associated with increased ER, expression. CONCLUSIONS Expression of TLR9 is increased in prostate cancer specimens, especially in the most poorly differentiated forms. Prostate 70: 817,824, 2010. © 2010 Wiley-Liss, Inc. [source] Metal-based antitumor, cytotoxic and antimicrobial activity: pharmacological evaluation of Knoevenagel condensate ,-diketone Schiff base thiosemicarbazone Cu(II) and Zn(II) complexesAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 7 2009N. Raman Abstract Knoevenagel condensate Schiff base ligands [L = 3-cinnamalideneacetylacetone-thiosemicarbazone (CAT)/3-cinnama- lideneacetylacetoneethylthiosemicarbazone (CAET)/3-cinnamalideneacetylacetonephenylthiosemicarbazone (CAPT)] and their copper/zinc complexes were synthesized. They were characterized by analytical and spectral techniques. From these data it was found that the ligands adopt square-planar geometry on metalation with Cu2+ and Zn2+. To evaluate the antitumor and cytotoxic activity of the synthesized complexes in mice and human cancer cell lines, the antitumor activity of the complexes was evaluated against an Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time and short-term in vitro cytotoxic activity. Oral administration of complexes (100 mg/kg) increased the survival time. The cytotoxic activity of complexes was evaluated using human breast cancer (MDA-MB-231), colon cancer (HCT-116) and nonsmall lung cancer (NCI-H-23) cell lines. Both the complexes possessed significant antitumor and cytotoxic activity on EAC and human cancer cell lines. The in vitro antimicrobial screening effect of the investigated compounds was also tested against the various organisms by well diffusion method. Copyright © 2009 John Wiley & Sons, Ltd. [source] Platinum and Palladium-triazole Complexes as Highly Potential Antitumor AgentsARCHIV DER PHARMAZIE, Issue 4 2010Najim A. Al-Masoudi Abstract The palladium complexes [(dppe)Pd(L)2PdCl2], [(dppe)Pd(L)2PtCl2], [(dppp)Pd(L)2PdCl2], [(dppm) Pd(L)2NiCl2], and [(dppm)Pd(L)2SnCl4] 15,19 were prepared. The antiproliferative activity of the newly synthesized complexes as well as their previously prepared analogues 3,14 and 20,26 were screened against a large panel of human cancer cell lines derived from haematological CD4+ human T-cells containing an integrated HTLV-1 genome (MT-4). The complex 12a, b exhibited remarkable antiproliferative activity against MT-4, CD4+ human acute T-lymphoblastic leukemia (CCRF-CEM), human splenic B-lymphoblastoid cells (WIL-2NS), human acute B-lymphoblastic leukemia (CCRF-SB), skin melanoma (SK-MEL-28), and prostate carcinoma (DU145) cell lines (CC50 = 0.5 ,M, 0.4 ± 0.05 ,M, 0.6 ± 0.05 ,M, 0.4 ± 0.1 ,M, and 0.8 ± 0.2 ,M, respectively), meanwhile, 9a, b, 14a, b, and 23 showed significant activity against the CCRF-SB cell lines (CC50 = 0.6 ± 0.06 ,M, 0.7 ± 0.05 ,M, 0.6 ± 0.05 ,M, and 0.8 ± 0.15 ,M, respectively). Further, 19 exhibited activity against the CCRF-CEM cell line (CC50 = 0.4 ± 0.05 ,M). [source] Antitumoractive Endoperoxides from TriterpenesARCHIV DER PHARMAZIE, Issue 10 2009Anja Niesen Abstract A series of triterpene endoperoxides was synthesized and screened for antitumor activity in a panel of 15 human cancer cell lines by a sulforhodamine-B (SRB) assay. The compounds induce apoptosis and show excellent antitumor activity. [source] Synthesis of 5-Substituted 2-Methylbenzimidazoles with Anticancer ActivityARCHIV DER PHARMAZIE, Issue 1 2003Sh. I. El-Naem Abstract A series of compounds comprising the thiocarboximidopyrazolyl 5, the phenylpyrazolyl 6, the dimethylpyrazolyl 7, the nitrophenylpyrazolyl 8, the dimethyloxazolyl 9, the benzoxazepinyl 10, and pyrimidyl 11 a,c derivatives of 3-(2-methyl-1H -benzimidazol-5-ylazo)pentane-2, 4-dione was synthesized. Moreover, 5-amino-2-methylbenzimidazole (3) was reacted with phthalic anhydride or maleic anhydride in acetic acid or in toluene to produce 12,15. Treating 5, 6-diamino-2-methylbenzimidazole (16) with ethyl cyanoacetate or diethyl malonate or acetyl acetone leads to the formation of the benzodiazepine derivatives 17,20. The cytotoxic activity of the compounds 2, 7, 9, 10, and 11 was tested against 60 types of human cancer cell lines. Compounds 7 and 9 were found to be the most potent. [source] | ||||||||||||||||||||||||||||