共查询到20条相似文献,搜索用时 15 毫秒
1.
Jamal M. Arif Swapnali S. Sawant Khalid A. El Sayed Muhammad Kunhi Manogaran P. Subramanian Yunus M. Siddiqui Diaa T. A. Youssef Khalid Al-Hussain Mohammed N. Al-Ahdal Fahad Al-Khodairy 《Journal of natural medicines》2007,61(2):154-158
The marine-derived cembranoid sarcophine (1) and its sulfur-containing semisynthetic derivatives (2–6) were evaluated for anticancer potential using cell cycle progression markers. No effect on MCF-7 cell viability or apoptosis
was seen with these derivatives at concentrations of up to 100 μM after 72 h of incubation. At 100 μM, sarcophine and its
derivatives 2–5 arrested the MCF-7 cells in G0/G1 phase, with concomitant decrease in the cell populations at S and G2+M phases. MDA-MB-231
cells were not responsive to any of the derivatives. Our preliminary results suggest that the sulfur-containing derivatives
of sarcophine, especially 2 and 3, show potent and cell-specific antiproliferative activity. 相似文献
2.
The present study was designed to investigate the anticancer activity of 4,7-dimethoxyflavanone in vitro. When human breast cancer MCF-7 cells were treated with 4′,7-dimethoxyflavanone at various concentrations (1–200 μM) for
24 h, antiproliferative effects were first observed at 1 μM and the IC50 was 115.62 μM. Conversely, 4′,7-dimethoxyflavanone was not cytotoxic (measured as lactate dehydrogenase release in CHO-K1
cells) under the same conditions. MCF-7 cells exposed to the 4′,7-dimethoxyflavanone at the IC50 concentration showed cell cycle arrest and apoptosis. Compared to the respective control level, exposure to 4′,7-dimethoxyflavanone
resulted in a remarkable increase of small DNA fragments at the sub-G1 phase and an increase in the G2/M phase cell population.
Moreover, when 4′,7-dimethoxyflavanone treatment caused G2/M phase arrest, an increase in CDK1 together with an increase in
cyclin B was observed. Based on these results, 4′,7-dimethoxyflavanone may be a useful anticancer agent. 相似文献
3.
Although benzo(a)pyrene (BP) induces apoptosis in vitro in murine Hepa1c1c7 cells and in vivo indications of apoptosis in rat lung exist, related cellular mechanisms in human cells are not known. p53 protein participates in several apoptotic processes. We found that BP induces cell death in human MCF-7 breast adenocarcinoma cells at 48 and 72 h but not in human A549 lung carcinoma cells. BP did not induce measurable caspase-3-like protease activity or internucleosomal DNA fragmentation in either cell types. However, procaspase-7 cleavage in MCF-7 cells by BP-treatment indicates activation of caspase-7 meaning that apoptosis is most likely involved in BP-induced MCF-7 cell death. BP-7,8-dihydrodiol-9,10-epoxide (BPDE)–DNA adducts and level of p53 protein increased dose-dependently, but more extensively in MCF-7 cells. Phosphorylation of p53 protein at serines 15, 20, 46 and 392 increased in MCF-7 cells. Increase in phosphorylation at serine 392 was clear already at 24 h by 1 μM concentration of BP. Increase of phosphorylation at other sites occurred only with higher concentrations or at later time points in relation to the increase of p53 protein. These results suggest that serine 392 phosphorylation is the first stabilizing event of p53 associated with BP exposure and subsequent cell death in MCF-7 cells. 相似文献
4.
David Potter Thomas M. Clarius Alan S. Wright William P. Watson 《Archives of toxicology》1994,69(1):1-7
Farm raised rainbow trout (Oncorhynchus mykiss) were exposed by various routes to benzo(a)pyrene (BP) as a representative carcinogenic polycyclic aromatic hydrocarbon (PAH).
Following exposure of fish to the chemical by intraperitoneal (i.p.) injection, 32P-postlabelling studies indicated that non-feral trout were relatively resistant to the formation of BP-DNA adducts in liver.
No adducts were detected in fish exposed to single doses (20 mg/kg) of BP. Multiple exposures (e.g. 2×25 mg/kg) were necessary
in order for adducts to be detected, indicating that induction of the metabolising enzymes required for the bioactivation
of BP is necessary. These studies provided reference information on DNA adducts for comparison with data from subsequent experiments
at environmentally realistic low level exposures. Two types of low level aquatic exposure were carried out. The first procedure
exposed fish for 30 days to a nominally constant low level (1.2 and 0.4 μg/l) of a homogeneous dispersion of BP in water,
to simulate low level aquatic environmental exposures. Following 32P-postlabelling analysis of the liver DNA of exposed fish, BP-DNA adducts were not detected. In the second procedure, fish
were exposed to a constant low level of BP (ca. 0.5 μg/l) for 15 days then to a pulse (60 μg/l) which was allowed to naturally
decline (to ca. 2 μg/l) during a further 15 days. Following this exposure, significant levels of BP-DNA adducts were detected
in livers of trout. The effect of dietary exposures was investigated by feeding trout a diet containing either 58 μg or 288
μg BP per day for 6 days, equivalent to total doses of 43 mg/kg and 216 mg/kg. In both cases BP-DNA adducts were detected
in livers of exposed fish. The results provide useful information on the types of exposures to PAHs which may pose a genotoxic
risk to fish in the environment.
Received: 5 April 1994 / Accepted: 31 May 1994 相似文献
5.
Cytotoxic and genotoxic potentials of newly synthesized antiviral aminopyrazoloquinoline derivatives
Jamal M. Arif Mohammed Kunhi Manogaran P. Subramanian Adnan A. Bekhit Ola A. El-Sayed Khalid Al-Hussein Hassan Y. Aboul-Enein Fahad M. Al-Khodairy 《Medicinal chemistry research》2008,17(2-7):297-304
In the present study, we screened newly synthesized antiviral aminopyrazoloquinoline derivatives for their cytotoxic and genotoxic potential in human normal and breast cancer cell lines using apoptosis and DNA adducts biomarkers. The compounds, along with the well-known antiviral drug acyclovir, were incubated with the normal (MCF-10A, MCF-12A) and cancer (MCF-7, MDA-MB-231) cell lines at 10, 50, and 100 μM for 72 h at 37°C. The most potent antiviral methoxy derivative (compound 3) was found to be more cytotoxic in the normal breast epithelial cell lines (MCF-10A and MCF-12A) and MDA-MB-231 cell lines at 50 μM. MCF-7 cells were found to be almost completely resistant to all these compounds while MDA-MB-231 cell lines were significantly killed by apoptosis. Acyclovir was ineffective in all these cell lines. We further tested these compounds using modulation of benzo[a]pyrene (BP)-DNA adduct formation in these cell lines. An inverse correlation was found between the degree of apoptosis and BP-DNA adduct levels for most of these compounds, although this seems to be the case only with the cancer cell lines. Our results suggest that the newly synthesized antiviral compounds have an associated risk of cytotoxicity and/or genotoxicity compared to acyclovir. 相似文献
6.
N. K. Sathish P. GopKumar V. V. S. Rajendra Prasad S. M. Shanta Kumar Y. C. Mayur 《Medicinal chemistry research》2010,19(7):674-689
A series of new 1,3-dimethyl acridone derivatives were synthesized with different alkyl side chain (propyl and butyl) substitution
at N10-position and highly basic amine groups at terminal end of alkyl side chain. All the synthesized molecules were screened for
their cytotoxic activity against human breast adenocarcinoma (MCF-7) and human promyelocytic leukemia (HL-60) cell lines.
DNA binding constants (Ki) of selected compounds were determined with calf-thymus DNA. Results showed that the molecules 7, 8, 10, 11, 12, 13, 14, and 15 exhibited good cytotoxic activity with IC50 value <10 μM. Compound 14 having (β-hydroxyethyl) piperazine butyl side chain exhibited potent cytotoxic activity against MCF-7 cell line and DNA-intercalating
properties. Examination of the relationship between lipophilicity and acridone derivatives showed poor correlation. 相似文献
7.
The biological activity of G-quadruplex DNA binding papaverine-derived ligand in breast cancer cells
Rubis B Kaczmarek M Szymanowska N Galezowska E Czyrski A Juskowiak B Hermann T Rybczynska M 《Investigational new drugs》2009,27(4):289-296
Summary It was shown previously that the papaverine oxidation products 6a,12a-diazadibenzo-[a,g]fluorenylium derivative (ligand 1)
and 2,3,9,10-tetramethoxy-12-oxo-12H-indolo[2,1-a]isoquinolinium chloride (ligand 2) bind to guanine-quadruplexes (G4) of
single stranded G-rich 3′-overhangs of mammalian telomeric DNA. Here we show the biological activity of ligand 1. This compound
exhibit antiproliferative activity in MCF-7 cells (IC50 for ligand 1 = 14.16 ± 0.01 μM, 24 h, 1.158 ± 0.056 μM, 72 h. PCNA levels were not altered after treatment of MCF-7 cells
with concentrations of ligand 1 which, however, led to alterations in the cell cycle. 5 and 10 μM of the ligand 1 arrested
cells in the G0/G1 phase of the cell cycle and this led to a decrease of cells in the S phase. Intracellular accumulation
of ligand 1 was observed even after a cell passage and medium exchange in fluorescence microscopy while low concentrations
of ligand 1 (0.001 to 0.1 μM) inhibited telomerase activity as shown by TRAP assay. 相似文献
8.
We recently reported that co-administration to female mice of tamoxifen or 4-hydroxytamoxifen (4-OH-tamoxifen) with pentachlorophenol
(PCP), but not with 2,6-dichloro-4-nitrophenol (DNCP) results in strong intensification of a specific subgroup, termed group
I, of tamoxifen-DNA adducts in female mouse liver. As both PCP and DCNP are sulfotransferase inhibitors, we concluded that
the intensification of tamoxifen group I adducts is probably not due to inhibition of sulfation by these phenols of a tamoxifen
metabolite. Since epoxide derivatives of 4-OH-tamoxifen are potential candidates involved in tamoxifen-induced DNA damage,
the hypothesis was developed and tested that PCP inhibits epoxide detoxication. As 4-OH-tamoxifen metabolites were unavailable
to us, we employed indirect approaches to test this hypothesis. In the first set of experiments we determined whether PCP
would augment DNA adduct formation from the benzo[a]pyrene metabolite, 9-hydroxybenzo[a]pyrene (9-OH-BP), as 9-OH-BP-4,5-epoxide
is known to be involved in the metabolic activation of this compound. Female mice were given a single i.p. dose of 9-OH-BP
(50 μmol/kg) either alone or in combination with PCP (75 μmol/kg), and hepatic DNA adducts were measured 24 h later by nuclease
P1-enhanced bisphosphate 32P-postlabeling. Co-administration of PCP with 9-OH-BP resulted in a statistically significant 1.5- to 1.7-fold increase in
9-OH-BP adduct levels versus 9-OH-BP controls. In order to determine whether PCP inhibits the enzymatic detoxication of epoxides
in vitro, in a second set of experiments, the effects of PCP on liver microsomal epoxide hydrolase (mEH) and purified equine
liver glutathione S-transferase (GST) activities were studied using, respectively, styrene-7,8-oxide and 1-chloro-2,4-dinitrobenzene
(CDNB) as substrates. Incubation of mouse liver microsomes with PCP (10–100 μM) strongly inhibited (by 21–97%) mEH activity
in a dose-dependent manner, the IC50 being 35 μM. DCNP was ineffective as a mEH inactivator. PCP also inhibited purified equine liver GST activity, with an IC50 of 23.5 μM. Taken together, the results of this study strongly support the hypothesis that PCP inhibited enzymatic detoxication
of epoxides in vivo and in vitro. By this mechanism PCP would lead to enhancement of DNA damage caused by 9-OH-BP, and possibly
other drugs and their metabolites, which undergo epoxidation prior to DNA binding.
Received: 28 November 1995/Accepted: 12 March 1996 相似文献
9.
Zheng MS Lee YK Li Y Hwangbo K Lee CS Kim JR Lee SK Chang HW Son JK 《Archives of pharmacal research》2010,33(9):1307-1315
Twenty five compounds including ten triterpenes (1–3, 5–11), six flavonoids (12–15, 24, 25), five lignans (17, 18, 21–23), two butenyl clohexnone glycosides (19–20), one fructofuranoside (16) and one fatty acid (4) were isolated from the roots of Ulmus davidiana var. japonica. The structures of those compounds were identified by comparing their physicochemical and spectral data with those of published
in literatures. All the compounds were evaluated for DNA topoisomerase inhibitory activities and cytotoxicities. Among the
purified compounds, 4 and 19 showed more potent inhibitory acitivities (IC50: 39 and 19 μM, respectively) than camptothecin, as the positive control (IC50: 46 μM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC50: 0.1, 0.52, 0.47, 0.42, 0.17 μM and 17 nM, respectively), which were more potent than that of etoposide as positive control
(IC50: 20 μM). In A549 cell line, 5 and 6 showed cytotoxicities (IC50: 4 μM and 3 μM, respectively, with IC50 of camptothecin as positive control: 10.3 μM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC50: 4, 3 and 4 μM, respectively, with IC50 of camptothecin: 0.3 μM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC50: 19, 19 and 15 μM, respectively, with IC50 of camptothecin: 2 μM). 相似文献
10.
The effect of solvent polarity and lipophilicity on DNA adduct formation by polycyclic aromatic hydrocarbons in skin and
lung has been studied in CD1 mice exposed cutaneously in vivo to benzo(a)pyrene (∼0.01–7.0 μg/animal) in either tetrahydrofuran
or n-dodecane. The nature and amounts of DNA adducts, measured as 7R,8S,9R-trihydroxy-10S-(N2-deoxyguanosyl-3′-phosphate)-7,8,9,10-tetrahydrobenzo(a)pyrene, in relation to exposure dose and treatment regime was determined
by 32P-postlabelling. In skin DNA there was a linear relationship between exposure dose and adduct formation with both solvents,
though the amount of adduct formed was significantly lower from treatment with benzo(a)pyrene in n-dodecane than in tetrahydrofuran. The amounts of adducts measured in skin DNA ranged from 67 amol adducts/μg DNA at the lowest
exposure dose of benzo(a)pyrene in n-dodecane to 3.5 fmol adducts/μg DNA (1 adduct in 5 × 107 nucleotides to 1 adduct in 9 × 105 nucleotides) at the highest dose. In tetrahydrofuran the corresponding levels were 89 amol adducts/μg DNA (1 adduct in 3 × 107 nucleotides) to 16.9 fmol adducts/μg DNA (1 adduct in 2 × 105 nucleotides). DNA adducts could not be detected in lung tissue following cutaneous treatment of animals with benzo(a)pyrene
in n-dodecane. Cutaneous treatment of animals with benzo(a)pyrene in tetrahydrofuran, however, resulted in adducts in lung DNA
at a level of 88 amol/μg DNA from exposures only at the highest dose (6.72 μg/animal). The difference in octanol-water partition
coefficient, log Pow between n-dodecane compared to tetrahydrofuran is considered to be the most likely reason for the reduction in the bioavailability
of benzo(a)pyrene and/or its metabolites and hence the degree of genotoxicity in tissues. The results suggest that other paraffinic
hydrocarbon solvents may moderate the genotoxicity of polycyclic aromatic hydrocarbons in vivo. The assessment of the genotoxicity
in vivo of mixtures of compounds should be carried out on complete mixtures of substances of interest in order to take account
of these possible antagonistic or synergistic effects.
Received: 10 February 1999 / Accepted: 10 May 1999 相似文献
11.
Marjo Tampio Piia Markkanen Katja A. Puttonen Eveliina Hagelberg Hannu Heikkinen Kati Huhtinen Jarkko Loikkanen Maija-Riitta Hirvonen Kirsi H. Vähäkangas 《Toxicology letters》2009
Benzo(a)pyrene (BP) forms benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adducts in human breast adenocarcinoma MCF-7 cells, leading to p53 protein induction and phosphorylation. Although BP-induced apoptosis in rodent cells is known, it is still unclear in human cells. Here we have analyzed the effects of BP on p53 related apoptotic proteins, cell cycle and cell death in MCF-7 cells. PUMA-protein (p53 up-regulated modulator of apoptosis) levels were changed after BP exposure so that PUMA-α protein was statistically significantly increased whereas PUMA-β protein was statistically significantly decreased. PUMA-protein levels were also investigated in ZR-75-1 cells, where PUMA-α protein was statistically significantly increased. Cytochrome c, which is released from mitochondria during apoptosis to form the apoptosome, was increased in cytoplasmic fraction after BP exposure in MCF-7 cells. Increased apoptosis was also seen after 48 and 72 h BP exposure (2.5 and 5 μM). In addition, BP decreased dose dependently cell viability (2.5 and 5 μM) and increased ROS formation (1 and 10 μM). Our results suggest that PUMA-α protein is involved in BP-induced cell death most likely through a p53 dependent apoptotic pathway. 相似文献
12.
Jae-Young Choi Chang-Seob Seo Ming-Shan Zheng Chong-Soon Lee Jong-Keun Son 《Archives of pharmacal research》2008,31(11):1413-1418
Two coumarins (1 and 6), one flavan-3-ol (2), one fatty acid (3), and two lignan glycosides (4 and 5) were isolated from the EtOAc and CH2Cl2 extract of the bark of Tilia amurensis. Their chemical structures were identified by comparing their physicochemical and spectral data with those of published in
literatures. Compounds 4, 5, and 6 were isolated from Tilia genus for the first time. Compounds 2 and 3 showed potent inhibitory activity against both DNA topoisomerase I (IC50 values; 49 μM and 4 μM, respectively, with 18 μM of positive control compound, comptothecin) and DNA topoisomerase II (IC50 values; 13 μM and 3 μM, respectively, with 50 μM of positive control compound, etoposide). However, all compounds did not
showed cytotoxicity against the human colon adenocarcinoma cell line (HT-29), the human breast adenocarcinoma cell line (MCF-7),
and human liver hepatoblastoma cell line (HepG-2). 相似文献
13.
C. M. Viau Temenouga N. Guecheva F. G. Sousa C. Pungartnik M. Brendel J. Saffi João Antonio Pêgas Henriques 《Archives of toxicology》2009,83(8):769-775
In order to clarify the molecular mechanisms of Sn2+ genotoxicity, we evaluated the induction of strand breaks, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III
(Endo III) sensitive sites, and the interference with the repair of methyl methane sulfonate (MMS)-caused DNA damage in V79
Chinese hamster lung fibroblasts exposed to stannous chloride by comet assay. A concentration-related increase in the DNA
damage induced by 2 h SnCl2 treatment at a concentration range of 50–1,000 μM was observed (r = 0.993; P < 0.01). Significantly elevated DNA migration in relation to the control level was detected at doses 100, 500 and 1,000 μM
in normal alkaline and at doses 500 and 1,000 μM in modified (with Fpg and Endo III) comet assay. Although 50 μM SnCl2 concentration did not increase significantly the DNA migration by itself in comet assay, it was capable to inhibit the repair
of MMS-induced DNA damage during the post-treatment period of 24 h. Our results demonstrate the genotoxic and comutagenic
effects of stannous chloride in V79 cells. The inhibitory effect of Sn2+ on repair of MMS-induced DNA damage suggests that this metal can also interfere in DNA repair systems thus contributing to
increased mutation by shifting the balance from error-free to error-prone repair processes. 相似文献
14.
A series of novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl) benzene-sulfonamides were synthesized and screened
for their cytotoxic activity against human breast cancer cell line (MCF-7). Compounds 6, 7, 9, 10, 11, and 14 displayed significant activity against MCF-7 when compared to doxorubicin, which was used as a reference drug. The synergistic
effect of Gamma radiation for the most active derivatives 7, 9, and 11 was also studied and their IC50 values markedly decreased to 11.9 μM, 11.7 μM, and 11.6 μM, respectively. 相似文献
15.
The present work describes the synthesis, antimicrobial and cytotoxic activity of 2,4-thiazolidinedione-5-acetic acid amides
3a–n. The structures of the compounds were confirmed by IR, 1H, 13C NMR and elemental analysis. All compounds were tested for antimicrobial activity by twofold serial dilution technique. The
preliminary results revealed that the compound 3d exhibits promising antibacterial and antifungal activity. The cytotoxic (MTT) activity of 2,4-thiazolidinedione-5-acetic
acid amides were tested in four tumour cell lines. We found that compound 3j inhibited proliferation of HeLa, HT29, A549 and MCF-7 cell lines with IC50 values of 33, 35, 30 and 36 μM, respectively. 相似文献
16.
Congener specific effects by polychlorinated biphenyls on catecholamine content and release in chromaffin cells 总被引:3,自引:0,他引:3
Maria Donata Messeri Ulf Bickmeyer Frank Weinsberg Herbert Wiegand 《Archives of toxicology》1997,71(7):416-421
The effects of the non-planar polychlorinated biphenyl (PCB) congener 2,2′,4,4′-tetrachlorobiphenyl (2,4-TCB) and of the
coplanar PCB congener 3,3′,4,4′-tetrachlorobiphenyl (3,4-TCB) were investigated on the catecholamine content and release from
bovine adrenal chromaffin cells in culture. Each congener was tested at three concentrations (20, 50 and 100 μM) and two exposure
periods (24 h and 5 days). Catecholamine release induced by K+-stimulation as well as catecholamine content of Triton X-100 treated cell cultures were examined using high-performance liquid
chromatography (HPLC). 2,4-TCB showed dose- and time-dependent effects. 2,4-TCB at 100 μM reduced the K+-stimulated catecholamine release after 24 h of exposure. After 5 days of exposure, 2,4 TCB at 50 and 100 μM drastically reduced
the K+-stimulated catecholamine release. 3,4-TCB even at a concentration of 100 μM over exposure of either 24 h or 5 days had no
effects on the K+-stimulated secretion. When chromaffin cells, exposed to 2,4-TCB, were lysed with 0.5% Triton X-100, a dose- and time-dependent
reduction of the catecholamine content appeared. The 3,4-TCB did not reduce the catecholamine content. Conversely there seemed
to be a trend towards an increase in catecholamine content. Spontaneous release of catecholamines was strongly increased by
the non-planar 2,4 TCB, while the coplanar 3,4 TCB showed no effects on this parameter. Furthermore, the effects of 2,4 TCB
appeared to be reversible after replacing the highest concentration (100 μM) of the TCB-solution with culture-medium at the
end of the 24-h exposure. Thus, K+-stimulated catecholamine release and the catecholamine content of bovine adrenal chromaffin cells was effectively reduced
by the non-planar PCB congener whereas spontaneous catecholamine release was strongly increased. The coplanar PCB congener
was ineffective at the same conditions.
Received: 7 January 1997 / Accepted: 11 February 1997 相似文献
17.
Zhou GD Richardson M Fazili IS Wang J Donnelly KC Wang F Amendt B Moorthy B 《Toxicology and applied pharmacology》2010,249(3):224-230
Carcinogen-DNA adducts could lead to mutations in critical genes, eventually resulting in cancer. Many studies have shown that retinoic acid (RA) plays an important role in inducing cell apoptosis. Here we have tested the hypothesis that levels of carcinogen-DNA adducts can be diminished by DNA repair and/or by eliminating damaged cells through apoptosis. Our results showed that the levels of total DNA adducts in HepG2 cells treated with benzo(a)pyrene (BP, 2 μM) + RA (1 μM) were significantly reduced compared to those treated with BP only (P = 0.038). In order to understand the mechanism of attenuation of DNA adducts, further experiments were performed. Cells were treated with BP (4 μM) for 24 h to initiate DNA adduct formation, following which the medium containing BP was removed, and fresh medium containing 1 μM RA was added. The cells were harvested 24 h after RA treatment. Interestingly, the levels of total DNA adducts were lower in the BP/RA group (390 ± 34) than those in the BP/DMSO group (544 ± 33), P = 0.032. Analysis of cell apoptosis showed an increase in BP + RA group, compared to BP or RA only groups. Our results also indicated that attenuation of BP-DNA adducts by RA was not primarily due to its effects on CYP1A1 expression. In conclusion, our results suggest a mechanistic link between cellular apoptosis and DNA adduct formation, phenomena that play important roles in BP-mediated carcinogenesis. Furthermore, these results help understand the mechanisms of carcinogenesis, especially in relation to the chemopreventive properties of nutritional apoptosis inducers. 相似文献
18.
Posser T de Aguiar CB Garcez RC Rossi FM Oliveira CS Trentin AG Neto VM Leal RB 《Archives of toxicology》2007,81(6):407-414
Pb(II) is a neurotoxic pollutant that produces permanent cognitive deficits in children. Pb(II) can modulate cell signaling
pathways and cell viability in a variety of cell types. However, these actions are not well demonstrated on glial cells, which
represent an important target for metals into the central nervous system. The present work was undertaken to determine the
ability of Pb(II) in modulating the activity of mitogen activated protein kinases (MAPKs) in cultures of C6 rat glioma cells,
a useful functional model for the study of astrocytes. Additionally, cell viability was analyzed by measurement of MTT reduction.
Cells were exposed to lead acetate 0.1, 1, 10 μM for 24 and 48 h. MAPKs activation—in particular ERK1/2, p38MAPK and JNK1/2—were analyzed by western blotting. Results showed that 10 μM Pb(II) treatment for 24 h caused a discrete stimulation
of p38MAPK phosphorylation. However, 1 and 10 μM Pb(II) treatment for 48 h provoked a significant stimulation in the phosphorylation
state of p38MAPK and JNK1/2. The phosphorylation state of ERK1/2 was not modified by any Pb(II) treatment. Moreover, data indicate that at
48 h treatment even 1 μM Pb(II) can be cytotoxic, causing impairment on cell viability. Therefore, depending on a long incubation
period, a significant concomitant activation of p38MAPK and JNK1/2 by Pb(II) took place in parallel with the impairment of C6 glioma cells viability. 相似文献
19.
Cyclosporin A induces apoptosis in rat hepatocytes in culture 总被引:2,自引:0,他引:2
Irene D. Román Nieves Rodríguez-Henche Jesús A. Fueyo Jose A. Zueco César Menor Juan C. Prieto Luis G. Guijarro 《Archives of toxicology》1998,72(9):559-565
Cyclosporin A (CsA) at concentrations up to 1 μM induced apoptosis in a dose-dependent manner in cultured rat hepatocytes
for 48 h in the presence of insulin and epidermal growth factor (EGF). The effect of CsA was evidenced by the DNA fragmentation
pattern constituted by fragments of multiples of 180–200 base pairs, which is a characteristic of programmed cell death. The
metabolic activity did not change significantly in the presence of 0.1 μM CsA and diminished to 49% of control in the presence
of 1 μM CsA. Changes in the metabolic activity were correlated with a decrease in both [methyl-3H]thymidine uptake and DNA content, which reflects a decrease in the cell number. The treatment of cells with CsA (1 μM) decreased
the metabolic activity/DNA content ratio by 24% with respect to dimethyl sulphoxide (DMSO) control, which also suggests, under
these conditions, that the necrosis achieved is at most only 24%. In addition, the changes observed (apoptotic process, arrest
of the cell cycle and apparition of a necrotic process) were correlated with an increase in the high-affinity guanosine triphosphatase
(GTPase) enzymes.
Received: 17 February 1998 / Accepted: 20 April 1998 相似文献
20.
Kim JS Lee SI Park HW Yang JH Shin TY Kim YC Baek NI Kim SH Choi SU Kwon BM Leem KH Jung MY Kim DK 《Archives of pharmacal research》2008,31(4):415-418
Five compounds were isolated from the chloroform-soluble fraction of the methanolic extract of the dried rhizomes of Zingiber officinale (Zingiberaceae) through repeated column chromatography. Their chemical structures were elucidated as 4-, 6-, 8-, and 10-gingerols,
and 6-shogaol using spectroscopic analysis. Among the five isolated compounds, 6-shogaol exhibited the most potent cytotoxicity
against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells. 6-shogaol inhibited proliferation of the transgenic mouse ovarian
cancer cell lines, C1 (genotype: p53-/-, c-myc, K-ras) and C2 (genotype: p53-/-, c-myc, Akt), with ED50 values of 0.58 μM (C1) and 10.7 μM (C2). 相似文献