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PubMed1996

Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants.

Gene expression of human immunodeficiency virus (HIV) depends on a host cellular transcription factors including nuclear factor-kappaB (NF-kappaB). The involvement of reactive oxygen intermediates (ROI) has been implicated as intracellular messengers in the inducible activation of NF-kappaB. In this study, we compared the efficacy of two antioxidants, alpha-lipoic acid (LA) and N-acetylcysteine (NAC), which are widely recognized NF-kappaB inhibitors. Here, we demonstrate that LA has a more potent activity in inhibiting NF-KappaB-mediated gene expression in THP-1 cells that have been stably transfected with a plasmid bearing a hygromycin B resistance gene under the control of HIV-1 long terminal repeat (LTR) promoter. The spontaneous activation of NF-kappaB in this cell culture system leads to expression of the hygromycin phosphotransferase gene hence rendering the cells resistance to hygromycin B. In this study, the effect of the test compounds against transcriptional activity of HIV-1 LTR was evaluated based on the degree of cellular toxicity due to the inhibitory activity on the expression of hygromycin B resistance gene in the presence of hygromycin B. We also found that 0.2 mM LA could cause 40% reduction in the HIV-1 expression from the TNF-alpha-stimulated OM 10.1, a cell line latently infected with HIV-1. On the other hand, 10 mM NAC was required to elicit the same effect. Furthermore, the initiation of HIV-1 induction by TNF-alpha was completely abolished by 1 mM LA. These findings confirm the involvement of ROI in NF-kappaB-mediated HIV gene expression as well as the efficacy of LA as a therapeutic regimen for HIV infection and acquired immunodeficiency syndrome (AIDS). Moreover, this study validates the applicability of our present assay system which we primarily designed for the screening of candidate drugs against HIV-1 gene expression.

Acetylcysteine↗

PubMed1996

Cytotoxic effects of 1 alpha,25-dihydroxyvitamin D3 and synthetic vitamin D3 analogues on a glioma cell line.

1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(OH)2D3) has recently been reported to exert a toxic effect on both rat and human glioma cell lines. However the potential clinical use of 1 alpha,25(OH)2D3 in the treatment of glioma is impaired by its potent hypercalcemic effects. We have therefore investigated the effects on glioma cell growth of several vitamin D3 analogues which have previously been shown to be less calcemic in vivo than 1 alpha,25(OH)2D3. The present study shows that several analogues are able to induce, in vitro, the death of rat glioma cells (C6.9). The compound KH 1060 appears to be the most effective in the induction of cell death, while MC 1288 and CB 1093 are as potent as 1 alpha,25(OH)2D3. EB 1089 was somewhat less effective than 1 alpha,25(OH)2D3 and MC 903, which is currently used in the treatment of psoriasis, has only a weak activity on C6.9 cells. The effective doses used are around 10(-9) M for 1 alpha,25(OH)2D3 and 10(-10) M for KH 1060. Interestingly, the toxic effect exerted by 1 alpha,25(OH)2D3 and its analogues is accompanied by several of the biochemical features of apoptosis, such as DNA fragmentation and induction of the c-myc protooncogene. These findings, together with the fact that the therapies currently available for glioma are only palliative, suggest that 1 alpha,25(OH)2D3 analogues such as KH 1060, EB 1089 or CB 1093, alone or in combination with other therapeutic approaches, could be of potential interest in the treatment of brain glial tumors.

Animals↗

PubMed2004

Platinum complex cytotoxicity tested by the electrical resistance breakdown assay.

The electrical resistance breakdown assay provides a novel approach for the quantification of cytotoxic activity of platinum based anticancer drugs. It is a functional assay system for cancer cell invasion that detects nanoscale alterations of an epithelial test barrier prior to microscopic morphometric changes. We measured changes in transepithelial electrical resistance (TEER) of a tight epithelial MDCK-C7 monolayer in response to highly invasive amelanotic melanoma cells (A7-clone) in combination with different platinum complexes (cis-, oxali- and carboplatin). The efficiency of the electrical resistance breakdown assay was compared a standard method for measurement of cytostatic activity, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The MTT-assay utilizes mitochondrial enzymatic activity to draw conclusions from a functional cell metabolism to the number of living cells in a sample. When human melanoma cells were seeded on top of an electrically tight MDCK-C7 monolayer, electrical leakage occurred within 48 h of co-culture. Electrical resistance breakdown was effectively prevented by cisplatin and its analogs (no significant difference between 100 microM cisplatin and corresponding controls with non-invasive cells). The results of the electrical resistance breakdown and MTT-assay were linearly dependent. Significance of both tests was equivalent, but the electrical resistance breakdown assay gave additional functional information. Compared to oxali- and carboplatin, cisplatin was more effective in preventing TEER-breakdown than reducing the number of tumor cells, giving rise to the assumption that cisplatin can reduce tumor cell number as well as invasiveness. In conclusion the electrical resistance breakdown assay provides a sensitive, continuous and cell-based assay system for the quantification of cancer cell invasiveness and evaluation of chemotherapeutics under physiological conditions.

Animals↗

PubMed2004

Differentiation of HL-60 myeloid leukemia cells induced by all-trans retinoic acid is enhanced in combination with caffeic acid.

We investigated a possible enhancement of all-trans retinoic acid (ATRA)-induced differentiation of HL-60 human myeloid leukemia cells by caffeic acid (CA), a widely distributed plant phenolic compound. Our results showed that CA, in the concentration of 13 or 52 micro M, had no or minimal influence on cell differentiation, whereas the differentiating activity of ATRA was potentiated by CA treatment. We proved, using flow cytometric detection of the CD66b surface molecule, a synergistic effect of CA: at day 10, 18.3% of CD66b-positive cells were detected after treatment with ATRA only, and 33% when CA and ATRA were combined together. NBT-assay confirmed that this additive effect of CA on ATRA-induced differentiation. Proliferating activity as assessed by MTT-assay was generally not affected by CA at given concentrations. However, cell proliferation was significantly reduced by 52 micro M CA at 96-h intervals. This effect was markedly enhanced when CA, at both concentrations, and ATRA were combined. The possibility to enhance the differentiation potential of ATRA by CA may improve outcomes in the therapy of acute promyelocytic leukemia.

Antigens, CD↗

PubMed1993

Effects of 1,1-dichloroethene and of some of its metabolites on the functional viability of mouse hepatocytes.

1,1-Dichloroethene (DCE) is hepatotoxic in rodents, and the expression of its toxicity involves probably its metabolism. In this study the role of DCE metabolites in the generation of the hepatotoxic lesion was investigated. Hepatocytes from male BALB/c mice in suspension were used as the experimental model. Cells were incubated with DCE for up to 5 hr and cellular viability was assessed by measurement of the release of lactate dehydrogenase into the medium and by alterations in the reduction of the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. After incubation for 3 hr DCE at 0.5 mM caused maximal toxicity, whereas at 0.1 mM DCE was only marginally toxic. Cytotoxicity was exacerbated by pretreatment of mice with buthionine sulfoximine (1.6 g/kg), an inhibitor of glutathione biosynthesis, given 4 hr prior to hepatocyte isolation. Inclusion of N-acetylcysteine (10 mM) into the incubate protected cells against DCE-induced cytotoxicity. Coincubation with octylamine (0.5 mM), an inhibitor of cytochrome P450, abolished the cytotoxic potential of 0.5 mM DCE during incubation for 3 hr. DCE toxicity was increased in hepatocytes from mice which had received ethanol or acetone in their drinking water, both of which induce levels of the hepatic cytochrome P450 isozyme P450 2E1. Incubation of cells with the P450 2E1 inhibitors N,N-dimethylformamide (10 mM) or diethyldithiocarbamate (100 microM) protected liver cells against the detrimental effect of DCE. Pretreatment of animals with phenobarbital, which induces the P450 2B subfamily, or 3-methylcholanthrene, which induces P450 1A1, did not affect the degree of hepatocytotoxicity elicited DCE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

3-OH flavone inhibition of epidermal growth factor-induced proliferaton through blocking prostaglandin E2 production.

Epidermal growth factor (EGF) has been shown to induce proliferation in cells, however, the role of prostaglandin E(2) (PGE(2)) plays in EGF-induced proliferation in still unclear. EGF and PGE(2) showed proliferation responses in epidermoid carcinoma cell A431 by MTT and [(3)H] thymidine incorporation assay. Activation of the EGF receptor and extracellular signal-regulated protein kinases (ERK1/2), but not p38 and JNK, appeared 10 min after EGF treatment, whereas total amounts of ERK1/2, p38 and JNK remained unchanged in A431 cells, accompanied by induction of COX-2 and PGE(2) production. PD98059, a specific ERK1/2 inhibitor, inhibited EGF-induced proliferation with concomitant decreases in ERK1/2 phosphorylation and COX-2/PGE(2) induction. Non-steroid anti-inflammatory drugs (NSAIDs) such as aspirin and diclofenac, a COX activity inhibitor, inhibited EGF-induced proliferation by blocking PGE(2) production. The addition of PGE(2) reversed the inhibitory effects of PD98059, aspirin, and diclofenac on EGF-induced proliferation. This suggests that COX-2/PGE(2) activation involves in EGF-induced proliferation and locates at the downstream of ERK1/2 activation. Furthermore, the natural product, 3-OH flavone, showed the most-potent inhibitory activity on EGF-induced proliferation among 9 structurally-related compounds, and suppression of EGF receptor phosphorylation, ERK1/2 phosphorylation, and COX-2/PGE(2) production by 3-OH flavone was identified. PGE(2) addition attenuates the inhibitory activity of 3-OH flavone on EGF-induced proliferation by MTT assay and colony formation by soft agar assay. Additionally, 3-OH flavone also showed more-specific inhibition on EGF- than on fetal bovine serum (FBS)-induced proliferation in A431 cells. Results of our present study provide evidence to demonstrate that PGE(2) is an important downstream molecule in EGF-induced proliferation, and 3-OH flavone, which inhibits PGE(2) production by blocking MAPK cascade, might reserve potential for development as an anti-cancer drug.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

Effect of aluminum and lead salts on lipid peroxidation and cell survival in human skin fibroblasts.

The aim of this study was to see whether aluminum (Al) and lead (Pb) salts are toxic for cultured human fibroblasts under different experimental conditions, in the controllable situation offered by cell cultures. Cell survival and membrane lipid peroxidation served as markers of Al and Pb toxicity. Evaluation of the living cells was carried out using a colorimetric method, the mitochondrial reduction of 1-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Lipoperoxidation assay was performed on whole cell homogenates by measuring thiobarbituric acid-reactive substances (TBARS) produced after incubation with ascorbic acid-ferrous sulfate. Al(III) and Pb(II) salts (300 microM) produce a considerable decrease in cell survival after an exposure period of 4d, evident with the three fetal calf serum concentrations in the culture media: 2, 5, and 10%. Taking into account in vitro cell aging, the cytotoxic effects of Al(III) and Pb(II) are greater in senescent fibroblasts than in young cells. Lead-induced cytotoxicity is higher than Al-induced cytotoxicity. A mechanism that contributes to cellular toxicity is membrane lipid peroxidation; our results demonstrate that Al(III) and Pb(II) ions, 400 microM, exert an antioxidant-like effect or a pro-oxidant action on cell membranes depending on exposure time. We describe significant increases in TBARS formation associated with the presence of 400 microM Al(III) or Pb(II) salts in the culture media. Our study also revealed that these heavy metals induce a cell age-dependent action on membrane lipoperoxidation that is greater in senescent fibroblasts and this could have severe consequences for maintenance of cellular integrity.

Aluminum Compounds↗

PubMed2000

Redox and fungicidal properties of phthalocyanine metal complexes as related to active oxygen.

Some chemical and fungicidal effects of 20 phthalocyanines of Co, Fe, Cu, and Al were studied. Under dark conditions, these complexes reduced nitroblue tetrazolium in the presence of KCN, accelerated the autoxidation of ascorbate or hydroquinone and decomposed hydrogen peroxide. In the later reaction, hydroxyl radical was generated as evidenced with the deoxyribose assay. The inhibition by superoxide dismutase and catalase of catalyzed autoxidation of ascorbate suggests the participation of superoxide anion-radical and hydrogen peroxide in the reaction. Most complexes were toxic to the fungus Magnaporthe grisea which causes blast disease of rice. The toxicity was enhanced by light being diminished by antioxidant reagents sequestering active oxygen species. Some complexes (including nontoxic ones), after 1-day contact with a leaf surface of the disease-susceptible rice cultivar, induced the fungitoxicity of leaf diffusate. This toxicity was also light-activated and sensitive to antioxidant reagents. Several complexes, when added to inocula, decreased 2-3 times the frequency of the compatible symptoms of the blast. It is suggested that in planta, the dark redox activity of phthalocyanines along with their photosensitization promote the generation of active oxygen, which damages the parasite and, therefore, favors disease resistance.

Antioxidants↗

PubMed2006

Cytotoxicity of materials used in perforation repair tested using the V79 fibroblast cell line and the granulocyte-macrophage progenitor cells.

AIM: To compare the cytotoxicity of materials used to repair perforations using permanent V79 fibroblasts and murine granulocyte-macrophage progenitor cells (CFU-GM). METHODOLOGY: Set specimens from amalgam, glass-ionomer, SuperEBA, N-Rickert, MTA and gutta-percha were eluted with culture medium for 72 h and their cytotoxicities were assessed by incubating the extracts with V79 and bone marrow-derived progenitors for 24 h and 7 days, respectively. Cytotoxicity on V79 cells was judged using the total nucleic acid content (NAC), neutral red uptake (NRU) and reduction of the tetrazolium salt (MTT). The number of bone marrow CFU-GM colonies determined in clonal cultures stimulated with recombinant murine granulocyte-macrophage colony-stimulating factor was used to assess cytotoxicity to progenitor cells. Statistical analyses were conducted using the one-way analysis of variance and Tukey's test where appropriate. RESULTS: All materials were cytotoxic in both cell systems; however, CFU-GM was more sensitive to the extracts than V79 cells. A similar rank order of toxicity was observed in V79 cells using the NAC and the MTT assays: glass-ionomer > N-Rickert congruent with SuperEBA > gutta-percha > amalgam congruent with MTA (P < 0.05). In contrast, the NRU test exhibited a lower sensitivity to MTA, gutta-percha and amalgam extracts. In the clonal culture assay, the toxicity was less pronounced in the presence of gutta-percha, SuperEBA and MTA. Similar cellular responses were found by placing the set specimens directly in the clonal culture dishes. CONCLUSIONS: The sensitivity of toxicity depended on the choice of the endpoint and the cell-culture system. Nevertheless, MTA was ranked as the least cytotoxic cement in both cell systems.

Acrylic Resins↗

PubMed2005

Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease.

Tyrosinase is a key enzyme in the synthesis of melanin in skin and hair and has also been proposed to contribute to the formation of neuromelanin (NM). The presence of NM, which is biochemically similar to melanin in peripheral tissues, identifies groups of neurons susceptible in Parkinson's disease (PD). Whether tyrosinase is beneficial or detrimental to neurons is unclear; whilst the enzyme activity of tyrosinase generates dopamine-quinones and other oxidizing compounds, NM may form a sink for such radical species. In the present study, we demonstrated that tyrosinase is expressed at low levels in the human brain. We found that mRNA, protein and enzyme activity are all present but at barely detectable levels. In cell culture systems, expression of tyrosinase increases neuronal susceptibility to oxidizing conditions, including dopamine itself. We related these in vitro observations to the human disease by assessing whether there was any genetic association between the gene encoding tyrosinase and idiopathic PD. We found neither genotypic or haplotypic association with three polymorphic markers of the gene. This argues against a strong genetic association between tyrosinase and PD, although the observed contribution to cellular toxicity suggests that a biochemical association is likely.

Adult↗

PubMed2000

Diazenes as modificators of drug-resistance in tumor cells.

To overcome the drug resistance, which is the major obstacle in the successful treatment of cancer patients, various compounds have been tested. Glutathione is one of the most promising targets for modulation. In the present study, we examined the influence of five new synthesized compounds--diazenes on the reduction of the intracellular level of GSH. Further, we investigated their ability to increase the cytotoxicity of cisplatin, vincristine and doxorubicin. In experiments human parental cervical (HeLa) and laryngeal (HEp2) carcinoma cells and their drug-resistant cell sublines (HeLaCA and CK2, respectively) were used. Intracellular GSH content was examined spectrophotometrically by the procedure developed by Tietze. The cell sensitivity to drugs was determined using a modified colorimetric MTT assay. Results showed that the rate of reduction of GSH concentration was dependent on the cell type and the type of diazenes. We did not find a correlation between the reduction in GSH level and increased cytotoxicity to selected anticancer drugs. Nevertheless, we found that: a) diazenes LV-35 and VZ-19 increased the cytotoxicity of cisplatin in HEp2 cells, b) diazene MG-19 potentiated the cytotoxicity of vincristine in HEp2 cells, and c) diazene VZ-19 in HeLaCA cells. These data suggest that specific combination of diazene and anticancer drug may be useful in the treatment of certain tumor types.

Antineoplastic Agents↗

PubMedDate not supplied

Induction of apoptosis in MCF-7 human breast cancer cells by phytochemicals from Anoectochilus formosanus.

The antitumor activity of Anoectochilus formosanus Hayata (Orchidaceae), a popularly used folk medicine in the treatment of cancers in Asia, was investigated in MCF-7 human mammary carcinoma cells. Plant extracts of A. formosanus were observed to induce apoptosis of MCF-7 cells as evidenced by cell-morphological changes, an early redistribution of plasma membrane phosphatidylserine, and DNA content distribution studies. Bioactivity-guided fractionation of A. formosanus extracts produced a specific ethyl acetate (EA)-partitioned fraction in which apoptotic activity was enriched. The chemical profile and candidate index compounds of the active EA fraction were obtained using HPLC and various spectral analyses. Western blot analysis showed that upon treatment of MCF-7 cells with the EA fraction, cleavage of pro-caspases-8, -9, and -7, and poly(ADP-ribose) polymerase as well as significant release of mitochondrial cytochrome c into the cytosol were readily observed. Flow cytometry showed that the Fas ligand protein was overexpressed in EA-treated MCF-7 cells. Functional genomic studies indicated that specific genes related to cytoskeleton rearrangement, apoptotic signal transduction, and various transcription factors were differentially regulated in EA-treated MCF-7 cells. Putative apoptotic signaling pathways of MCF-7 cells in response to the EA extract of A. formosanus are proposed.

Antineoplastic Agents, Phytogenic↗

PubMed2003

BM-573, a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, prevents pig myocardial infarction induced by coronary thrombosis.

The aim of this study was to characterize the effects of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a novel dual thromboxane A2 receptor antagonist and thromboxane synthase inhibitor, on myocardial infarction induced by topical ferric chloride (FeCl3) application to the left anterior descending (LAD) coronary artery in anesthetized pigs. All control animals (n = 6) developed an occlusive thrombus in the LAD coronary artery. The mean infarct size, revealed by triphenyl tetrazolium chloride (TTC), and the area at risk, evidenced by Evans blue, corresponded to 35.3 +/- 2.2 and 36.9 +/- 2.1% of the left ventricular mass, respectively. In the BM-573-treated group (n = 6), a drug infusion (10 mg. kg-1. h-1) started 30 min before FeCl3 application and continued throughout the experimentation. Among the BM-573-treated group, four pigs did not develop coronary artery thrombus and their myocardium appeared healthy. Histopathological examination of FeCl3-injured coronary artery revealed an occlusive and adherent thrombus in control group, while pretreatment with BM-573 prevented thrombus formation. In infarcted zones, lack of desmin staining and muscle structure disorganization were obvious. Depletion of myocardial ATP content was observed in the myocardial necrotic region of the control group, but not in myocardial samples of BM-573-treated pigs that did not develop myocardial infarction. When BM-573 prevented LAD artery occlusion, the area under the curve of plasmatic troponin T was reduced by 77% over 6 h. These data suggest that BM-573 could be useful for the prevention of myocardial infarction.

Animals↗

PubMedDate not supplied

Reduction of cisplatin toxicity in cultured renal tubular cells by the bioflavonoid quercetin.

Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of various bioflavonoids on CP toxicity in an in vitro model of cultured tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100-400 microM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3 h significantly reduced the extent of cell damage. The protective activity of QC was concentration dependent, starting at 10-25 microM and reaching a plateau between 50 and 100 microM. Other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations (100-500 microM). Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding 75 microM. Our data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells. The exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.

Animals↗

PubMed1999

Paracrine role of adventitial superoxide anion in mediating spontaneous tone of the isolated rat aorta in angiotensin II-induced hypertension.

The relationship between vascular generation of superoxide anion and spontaneous tone observed in the isolated aorta was studied in hypertensive rats infused with angiotensin II. Aortic rings from hypertensive, but not from sham-operated rats, demonstrated oscillatory spontaneous tone that represented 52+/-5.6% of the maximal contraction to KCl. Spontaneous tone was prevented by calcium-free buffer or by blocking calcium influx through L-type calcium channels with nifedipine. The production of superoxide anion measured by lucigenin chemiluminescence was up to 15-fold higher than in sham-operated rat aorta. The adventitial site of production of superoxide anion was suggested by the fact that lucigenin chemiluminescence was 5.5-fold higher from the adventitia than from the intima. This was confirmed histochemically by demonstrating that the adventitia was the site of reduction of nitroblue tetrazolium as well as immunohistochemical staining of NAD(P)H oxidase subunit proteins. A causal link between superoxide anion production by NAD(P)H oxidase and the spontaneous tone is suggested by the fact that superoxide dismutase or the inhibitor of NAD(P)H oxidase, diphenylene iodonium, decreased both superoxide anion production and spontaneous tone. L-NAME or removal of the endothelium from the aorta had no significant effect on superoxide anion levels or spontaneous tone. However, although superoxide dismutase decreased superoxide anion levels in the presence of L-NAME or in endothelium-denuded rings, it no longer inhibited the tone. This suggests that the effect on tone of superoxide anion originating in the adventitia is mediated by inactivating endothelium-derived nitric oxide, which promotes smooth muscle calcium influx and spontaneous tone. The adventitia is not a passive bystander during the development of hypertension, but rather it may have an important role in the regulation of smooth muscle tone.

Acridines↗

PubMed1996

Differentiation inducing effects of 2-chloro-3-amino-1,4-naphthoquinone on human leukemia HL-60.

There are some highly cytotoxic anticancer compounds inducing differentiation of cancer cells to normal cells at below highly cytotoxic concentration. Naphthoquinone derivatives having cytotoxic effects on cancer cell were tested to learn whether they have differentiation inducing activity in human leukemia HL-60 cells or not. When HL-60 cells were treated with 2-chloro-3-amino-1,4-naphthoquinone (CANQ) for four days, differentiation-related phenotypes such as nitrobluetetrazolium (NBT)-reducing ability and phagocytosis were induced. These differentiation markers were increased by cotreatment with 1,25-dihydroxyvitamin D3 which is a well-known inducer of differentiation in HL-60 cells. To evaluate the route of differentiation induced by CANQ, we examined naphthol AS-D chloroacetate esterase and alpha-naphthylacetate esterase activities and changes in cellular size and granulation. Treatment of HL-60 cells with CANQ for four days resulted in an 82.4% increase in alpha-naphthylacetate esterase activity in spite of a 0.2% increase in naphthol AS-D chloroacetate esterase activity. The size of cells in cell mass was larger and granulation was more decreased than untreated cells. These results indicate that HL-60 cells were induced to differentiate into macrophage-like cells.

Calcitriol↗

PubMed2001

In vitro effects of antiviral agents on human keratocytes.

PURPOSE: To study the effects of antiviral agents on human keratocytes in vitro. METHODS: Cultured human keratocytes were incubated with either ganciclovir, idoxuridine, trifluridine, or cidofovir at concentrations from 0.0001 to 10 mg/mL. Phase-contrast microscopy and XTT (sodium [2,3-bis [2-methoxy-4-nitro-5-sulphophenyl]-2h-tetrazolium-5-carboxanilide, inner salt) colorimetric assay were performed after 24, 48, and 72 hours of incubation. RESULTS: When adjustments were made for time of incubation and concentration, trifluridine reduced cell viability significantly more than ganciclovir, idoxuridine, and cidofovir (p<0.001, three-way analysis of variance). There was significant time-and dose-dependent reduction of cell viability (p<0.001) with trifluridine and cidofovir. After a 72-hour incubation with ganciclovir or idoxuridine, cell viability was reduced as compared with 24- and 48-hour incubation (p<0.001); only the effects of the highest concentration tested (1.0 mg/mL) were significantly different from those of the lower concentrations (p<0.002). At a concentration of 1.0 mg/mL, trifluridine and cidofovir produced moderate to severe signs of cytotoxicity, whereas ganciclovir and idoxuridine displayed much less severe morphologic signs. CONCLUSIONS: Our results indicate that antiviral agents may have both time- and concentration-related toxic effects on stromal keratocytes. These findings may impact the selection of the most appropriate antiviral drug when it is needed to treat infections involving the corneal stroma.

Antiviral Agents↗

PubMedDate not supplied

PM-3, a benzo-gamma-pyran derivative isolated from propolis, inhibits growth of MCF-7 human breast cancer cells.

Propolis has numerous biologic activities including antibiotic, antifungal, antiviral and anti-inflammatory properties. Several components isolated from propolis have been shown to have anticancer activity. This study demonstrates that the compound PM-3 (3-[2-dimethyl-8-(3-methyl-2-butenyl)benzopyran]-6-propenoic acid) isolated from Brazilian propolis markedly inhibits the growth of MCF-7 human breast cancer cells. This effect was associated with inhibition of cell cycle progression and induction of apoptosis. Treatment of MCF-7 cells with PM-3 arrested cells in the G1 phase and resulted in a decrease in the protein levels of cyclin D1 and cyclin E. PM-3 also inhibited the expression of cyclin D1 at the transcriptional level when examined in cyclin D1 promoter luciferase assays. Induction of apoptosis by PM-3 occurred within 48 hours after treatment of MCF-7 cells. The MCF-7 treated cells also displayed a decrease in the level of the estrogen receptor (ER) protein and inhibition of estrogen response element (ERE) promoter activity. Therefore, PM-3 merits further investigation with respect to breast cancer chemoprevention or therapy.

Annexin A5↗