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PubMed1998

Apoptosis and necrosis during ischaemia in renal tubular cells (LLC-PK1 and MDCK).

BACKGROUND: Ischaemia is the most frequent cause of acute renal failure. It has been previously demonstrated that ischaemia is connected with signs of necrosis and apoptosis. Apoptosis is an energy-dependent process. During ischaemia intercellular energy levels decline rapidly. Therefore, the goal of the investigation was to reveal the time dependency of cell death mechanisms during ischaemia leading to irreversibility of tissue damage. METHODS AND RESULTS: A model of renal ischaemia induced by ATP depletion was used in LLC-PK1 and MDCK-cells. Cell proliferation, determined by 3H-thymidine and BrdU incorporation and by the Ki67-labelling index was affected already after 1-2 h of ATP depletion in both cell lines. Cell viability and membrane leakage, estimated by trypan blue and propidium iodide exclusion and LDH release, was profoundly increased after 8-16 h. Evaluation of mechanisms of necrotic or apoptotic cell death was calculated from fraction of cells with pyknotic nuclei, investigation of DNA fragmentation and, by translocation of phosphatidylserine (PS) from the inner membrane face to the surface. In both cell lines increased numbers of cells with condensed nuclei was not a major sign of apoptosis. Only in MDCK cells were the numbers of cells with condensed nuclei significantly increased after 1 h compared to controls. As a hallmark of apoptosis, ATP depletion resulted in intranucleosomal DNA fragmentation after 1 h. After 8-16 h this pattern changed to a smear pattern, as a sign for necrosis. PS staining was detectable at the cell surface after 1 h. CONCLUSIONS: Ischaemia is associated with a rapid loss of proliferation and signs of apoptosis at early stages in a small proportion of cells. Most cells undergo the necrotic pathway of cell death after prolonged ATP depletion (8 h). There was no difference in behaviour comparing proximal (LLC-PK1) with more distal (MDCK) cell culture models. These results may help to explain the findings that apoptosis and necrosis have both been described after renal ischaemia.

Animals↗
PubMed1990

Analysis of sperm cell viability, acrosomal integrity, and mitochondrial function using flow cytometry.

A triple staining procedure was developed to evaluate bull spermatozoa using flow cytometry. Flow cytometric estimates of cell viability, measured by propidium iodide (PI) exclusion, and acrosomal integrity, measured by Pisum sativum agglutinin (PSA) binding acrosomal contents, were equivalent to estimates made by using standard laboratory assays. Mitochondrial function, measured by rhodamine 123 (R123) fluorescence, was depressed by the mitochondrial inhibitors rotenone (64%) or monensin (52%), establishing that mitochondrial damage can be detected. Dilauroylphosphatidylcholine (PC12) or lysophosphatidylcholine (LPC) was used to destabilize sperm membranes. When challenged with 15-30 microM PC12, selective exposure of PSA binding sites occurred without induction of PI uptake or loss of R123 staining. However, PC12 concentrations greater than 60 microM resulted in a loss of R123 fluorescence intensity. In contrast, greater than 1200 microM LPC was required to expose PSA binding sites, which also resulted in PI uptake. By using flow cytometry, these three stains in combination can be used to correlate three different features simultaneously on individual spermatozoa and assay thousands of cells per sample without extensive preparation.

Acrosome↗
PubMed1997

Fluorometric assessments of mitochondrial function and viability in cryopreserved bovine spermatozoa.

Mitochondrial function and sperm viability were quantified in samples of cryopreserved bovine spermatozoa from 12 bulls using fluorometric techniques. The active mitochondria of the spermatozoa were fluorescently stained using three different fluorophores: rhodamine 123 (R123), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyan ine iodide (JC-1) or MitoTracker Green FM (MITO). The stained spermatozoa, and companion aliquots that had been stained with SYBR-14 (a living-cell nucleic acid stain) and propidium iodide to assess viability, were quantified using flow cytometry. The resulting fluorescent measurements of mitochondrial function were compared with microscopic assessments of progressive sperm motility immediately after thawing, with motility after 3-h incubation at 37 degrees C, and with the fluorescent assessment of sperm viability. Staining with either R123 or MITO resulted in a single green population. In contrast, the JC-1 staining of mitochondria produced both green and red-orange populations of spermatozoa and sometimes a progressive gradient between the two populations. The ability of JC-1 to discriminate between mitochondria exhibiting high membrane potential from those having low to medium membrane potential provided a more rigorous estimate of metabolic function than the other two fluorescent stains. Overall, the three fluorometric measurements of mitochondrial function were highly correlated with each other, with the SYBR-14 assessment of viability, and with the microscopic estimates of motility.

Animals↗
PubMed2001

Ratio of proliferating cell nuclear antigen-positive nuclei to total cell number is higher in day 7 than in day 8 vitrified in vitro-produced bovine embryos.

The aim of the present study was to find a reliable functional criterion for the evaluation of the proliferation potential of bovine in vitro-produced embryos. We used immunocytochemical detection of proliferating cell nuclear antigen (PCNA) combined with propidium iodide (PI) staining and subsequent confocal laser scanning microscopy together with routine morphological evaluation under a stereomicroscope to study fresh Day 7, 8, and 9, and cryopreserved Day 7 and 8 embryos. The ratio of PCNA/PI-positive nuclei was equal in fresh Day 7 and Day 8 embryos and significantly lower in Day 9 embryos. In general, Day 7 embryos tolerated the cryopreservation treatments better than Day 8 embryos. Vitrification in normal straws was especially detrimental to Day 8 embryos. In fresh Day 7 and 8 embryos, the PCNA results were in agreement with stereomicroscopic evaluation. However, in Day 9 fresh and in Day 7 and 8 treated embryos, the missing PCNA revealed disorders that were not observed under morphological evaluation. PCNA immunocytochemistry is an effective method to obtain information about the functional state of nuclei. The ratio of PCNA-positive nuclei can provide more information and numerical data about the developmental potential of bovine embryos after cryopreservation.

Animals↗
PubMed2002

Sperm apoptosis in fresh and cryopreserved bull semen detected by flow cytometry and its relationship with fertility.

The present study was conducted to detect sperm apoptosis in fresh and frozen semen and to determine its relationship with bull fertility. Three ejaculates were collected from five breeding bulls with different fertility levels and were cryopreserved using standard methods. Two flow cytometric methods were employed to measure apoptosis: an assay for phosphatidylserine (PS) translocation across the plasma membranes using fluorescein-labeled Annexin V and propidium iodide (PI), and an assay for nicked DNA using bromodeoxyuridine (BrdU), terminal deoxynucleotidyl transferase, and fluorescein-labeled anti-BrdU monoclonal antibody. Both assays showed that fresh sperm contained 10%-20% apoptotic sperm. Significant differences in the percentage of apoptotic sperm were observed among the bulls. Cryopreservation induced translocation of PS to the outer leaflet of the plasma membrane and caused most of the necrotic cells in fresh sperm to disintegrate. Bull fertility was significantly related to the percentage of necrotic or viable sperm in fresh semen as detected by the Annexin V/PI assay, to the number of apoptotic sperm in fresh semen as detected by the TUNEL assay, and to the level of chromatin or DNA condensation as detected by PI staining. The present study suggests that the presence of apoptotic spermatozoa in fresh semen could be one of the reasons for poor fertility in breeding bulls.

Animals↗
PubMed2002

Apoptosis and cell proliferation potential of bovine embryos stimulated with insulin-like growth factor I during in vitro maturation and culture.

Reliable estimation and improvement of the developmental potential of in vitro production (IVP) embryos requires functional criteria of embryo quality. Antiapoptotic and mitogenic effects of insulin-like growth factor I (IGF-I), applied during bovine IVP, were studied. Day 6.5 blastocysts were fixed and processed for TUNEL to detect apoptotic cells, for immunocytochemical detection of proliferating cell nuclear antigen (PCNA), and for propidium iodide (PI) staining to detect all nuclei. Laser scanning confocal microscopy was used to determine apoptotic (TUNEL/PI) and proliferative (PCNA/PI) indices. Addition of IGF-I to the culture but not to the maturation medium increased the morula/blastocyst yield (P = 0.03), but the cleavage rate was not affected. During culture, IGF-I significantly lowered the apoptotic index by decreasing the number of apoptotic cells per embryo and elevated the total cell number of the blastocysts. The frequency of blastocysts with apoptotic cells was not affected. IGF-I increased the proportion of blastocysts with apoptotic cells in the inner cell mass area only by reducing apoptosis in the trophectoderm area. The PCNA index was not affected by IGF-I. A positive correlation observed between apoptotic and PCNA-positive cells was significant in groups stimulated with IGF-I during in vitro culture. Of TUNEL-positive cells, 30%-40% per embryo were also positive for PCNA. This colocalization may indirectly suggest an activation of DNA repair process in TUNEL-positive cells in response to DNA fragmentation. IGF-I reduces apoptosis in bovine IVP embryos. The requirement of IGF-I is more critical during embryo culture than during oocyte maturation. Our data suggest that an assay for TUNEL in conjunction with cell proliferation analysis can provide useful information about the quality of IVP embryos.

Animals↗
PubMed1999

Acute cell damage after low Mg2+-induced epileptiform activity in organotypic hippocampal slice cultures.

Upon perfusion with Mg2+-free artificial cerebrospinal fluid (ACSF) organotypic hippocampal slice cultures develop seizure-like events and tonic recurrent discharges in which areas CA3 and CA1 and, in contrast to acute slices, also the dentate gyrus (DG) participate. Using the fluorescent dye propidium iodide (PI) we show that sustained epileptic activity causes cell death in the DG and pyramidal cell layer particularly evident in the granule cell layer of the DG. This correlates with the decrease of the electrophysiological responses to hilar stimulation. Interestingly, perfusion with carbogenated serum-free ACSF also induces some cell death which is, however, mild compared with low magnesium treated slice cultures.

Animals↗
PubMed1999

Peripheral binding site is involved in the neurotrophic activity of acetylcholinesterase.

Acetylcholinesterase (AChE) catalyses the hydrolysis of the neurotransmitter acetylcholine and it has been implicated in several non-cholinergic actions, including neurite outgrowth and amyloid formation. We have studied the trophic function of brain AChE on neuronal cell metabolism and proliferation as well as the enzyme domain involved in such effects. Low AChE concentrations (0.1-2.5 nM) stimulated neurite outgrowth and induced cell proliferation as measured by MTT reduction and [3H]thymidine incorporation. The action of AChE was not affected by edrophonium and tacrine both active site inhibitors, but it was abolished by propidium and gallamine, two peripheral anionic binding site (PAS) ligands. We conclude that the PAS domain of AChE is involved in the neurotrophic activity of the enzyme.

Acetylcholinesterase↗
PubMed2000

Pyruvate protects against 3-nitropropionic acid neurotoxicity in corticostriatal slice cultures.

Previously, we have shown that 3-nitropropionic acid (NPA) neurotoxicity in organotypic corticostriatal slice cultures is dependent on glucose and glutamate. Here we studied the neuroprotective potential of agents improving mitochondrial function, including creatine, malate, oxaloacetate, Pyruvate and L-lactate in NPA-treated slice cultures. pyruvate provided the best protection against the loss of glutamic acid decarboxylase activity, depletion of GABA levels, increased propidium iodide uptake and increased glial fibrillary acidic protein levels. ATP levels were significantly reduced by 100 microM NPA (but not by 50 microM) and restored by pyruvate (5 mM). Creatine and L-lactate had no significant protective effect. Protective mechanisms of pyruvate are probably multifold, including stimulation of the citric acid cycle, scavenging and reduction of excitotoxicity.

Adenosine Triphosphate↗
PubMed2000

GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures.

The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN-containing medium significantly reduced the NMDA-induced PI uptake in the CA1 (p < 0.01), suggesting neuroprotective effects of these factors, beyond their well-known trophic effects on dopaminergic neurons.

Animals↗
PubMed2004

Inhibition of amyloid-beta-induced neurotoxicity and apoptosis by moderate ethanol preconditioning.

Consumers of moderate amounts of ethanol have a lower risk of Alzheimer's dementia than do abstainers. In Alzheimer's disease the brain contains many extracellular plaques composed of amyloid-beta (Abeta), a neurotoxic protein linked to pathogenesis of the disease. Here we report that moderate ethanol preconditioning (20-30 mM for 6 days) of organotypic hippocampal-entorhinal slice cultures prevents Abeta-induced neurotoxicity and apoptosis as measured by media lactate dehydrogenase levels and staining with propidium iodide and Hoechst 33342. With Abeta, as with our previous studies of the neurotoxic HIV-1 protein gp120, moderate ethanol preconditioning may interfere with various glial-mediated neurotoxic responses in the slices to Abeta. In addition, we found that moderate ethanol preconditioning causes an almost 3-fold increase in brain levels of heat shock protein 70 (hsp70), a protective molecular chaperone. Our results suggest possible molecular mechanisms underlying the protective effect of moderate drinking against Alzheimer's dementia.

Amyloid beta-Peptides↗
PubMed1997

In vitro combination effect of 5-fluorouracil and cisplatin on the proliferation, morphology and expression of Ki-67 antigen in human gastric cancer cells.

The combination effect of 5-fluorouracil (5-FU) and cisplatin was examined in terms of the proliferation, morphology and expression of Ki-67 antigen, and propidium iodide (PI) staining using four cultured human gastric cancer cell lines, and we assessed how such activity was affected by the exposure time and the timing of treatment. MKN-1, MKN-28, MKN-45 and MKN-74 cells were exposed to various concentrations of 5-FU for 72 h and cisplatin for 8 or 72 h. At IC50, MKN-28 cells were more sensitive to 5-FU than other cell lines, whereas MKN-1 and MKN-45 cells were more sensitive to cisplatin than other cell lines. The cell growth-inhibitory activity of cisplatin was found to be 'area under the curve' dependent. When 5-FU and cisplatin were combined simultaneously, the combination effect was higher than that of 5-FU or cisplatin alone. On the other hand, when cisplatin was applied before 5-FU, there was no potentiation of the cell growth-inhibitory activity by combination treatment. In 5-FU-treated MKN-74 cells, the size, morphology and PI staining of nuclei were almost the same as those of the untreated cells, and the expression of Ki-67 antigen was less than that of the untreated cells. In cisplatin-treated MKN-74 cells, the size of cells and nuclei was larger than that of the untreated cells and fragmentation of nuclei was observed. The expression of Ki-67 antigen was less than the untreated cells but more than that of 5-FU-treated cells. In the cells treated with 5-FU and cisplatin in combination, the above changes were an intermediate of those of 5-FU-treated cells and cisplatin-treated cells. In conclusion, the cell growth-inhibitory activity of 5-FU and cisplatin against gastric cancer cells was potentiated by the combined treatment with 5-FU and cisplatin simultaneously, but not with cisplatin followed by 5-FU.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Determination of the time course and extent of neurotoxicity at defined temperatures in cultured neurons using a modified multiwell plate fluorescence scanner.

The cellular and molecular mechanisms of hypoxic/ischemic neurodegeneration are sensitive to numerous factors that modulate the time course and degree of neuronal death. Among such factors is hypothermia, which can dramatically protect neurons from injury. To examine and control for temperature-dependent effects, we developed a technique that provides for a high-throughput, accurate, and reproducible determination of the time course and degree of neurotoxicity in cultured cortical neurons at precisely defined temperatures. We used a fluorescence multiwell plate scanner, modified by us to permit the control of temperature, to perform serial quantitative measurements of propidium iodide (PI) fluorescence in cortical neuronal cultures exposed to excitotoxic insults. In validating this approach, we show that these time course measurements correlate highly with manual counts of PI-stained cells in the same cultures (r = 0.958, p < 0.0001) and with lactate dehydrogenase release (r = 0.964, p < 0.0001). This method represents an efficient approach to mechanistic and quantitative studies of cell death as well as a high-throughput technique for screening new neuroprotective therapies in vitro.

Animals↗
PubMed1991

Effect of methotrexate on cell cycle and DNA synthesis of astrocytes in primary culture: flow cytometric studies.

Relatively pure population of astrocytes in primary culture were examined by flow cytometry at various time intervals after exposure to 1, 10 and 100 microM of methotrexate (MTX). The percentage population of cells in different phases of the cell cycle was determined using propidium iodide (PI) to measure cellular DNA content. DNA synthesis was assessed by measuring the fluorescence intensity of FITC-conjugated antibody to bromodeoxyuridine (BrdUrd). The two parameters were correlated to determine the location of BrdUrd-incorporating cells within the cell cycle. Exposure of astrocytes to MTX caused a consistent increase in number of cells in S-phase which correlated with the increase in BrdUrd incorporation. These studies provide supportive evidence that the astrogliosis seen in MTX encephalopathy may be due to a primary involvement of astrocytes.

Animals↗
PubMed2000

The selectivity and specificity of the actions of the lipido-sterolic extract of Serenoa repens (Permixon) on the prostate.

PURPOSE: To investigate the effects of the phytotherapeutic agent, Permixon(R), on primary cultures of fibroblast and epithelial cells from the prostate, epididymis, testes, kidney, skin and breast and to determine the selectivity and specificity of the action of the drug. MATERIALS AND METHODS: All primary cultures were examined by electron microscopy before and following treatment with Permixon(R) (10 microg./ml.). In addition the apoptotic index was assessed by flow cytometry employing propidium iodide as a fluorophore. The impact of the drug on 5alpha-reductase (5alphaR) isoenzymes was also tested utilizing a pH specific assay. RESULTS: There were changes in the morphology of prostate cells after treatment including accumulation of lipid in the cytoplasm and damage to the nuclear and mitochondrial membranes; no similar changes were observed in other cells. Permixon(R) increased the apoptotic index for prostate epithelial cells by 35% and 12% in the prostate stromal/fibroblast. A lesser apoptotic effect was demonstrated in skin fibroblast (3%) whereas none of the other primary cultures showed any increase in apoptosis when compared with the controls. Permixon(R) was also an effective inhibitor of both 5alphaR type I and II isoenzymes in prostate cells, but other cells showed no inhibition of 5alphaR activity following treatment with the plant extract. CONCLUSIONS: This investigation demonstrated the selectivity of the action of Permixon(R) for prostate cells. The morphological changes in the prostate are accompanied by an increase in the apoptotic index along with an inhibition in the activity of the nuclear membrane bound 5alphaR isoenzymes. No similar changes were observed in any of the other cells under investigation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1997

Prediction of drug cytotoxicity in 9L rat brain tumor by using flow cytometry with a deoxyribonucleic acid-binding dye.

OBJECTIVE: Flow cytometry (FCM) with a deoxyribonucleic acid (DNA)-binding dye, propidium iodide, provides a rapid and quantitative method to detect apoptotic cell death. This technique was used to examine the sensitivity of tumor cells to anticancer agents, as a novel test of chemosensitivity in vitro. METHODS: The in vitro chemosensitivity of 9L gliosarcoma cells to a panel of anticancer agents (cisplatin, nimustine, adriamycin, cyclophosphamide, vincristine, 5-fluorouracil, and methotrexate) was investigated by both FCM, yielding DNA histograms, and a microtiter tetrazolium test, measuring cellular metabolism. Clinically achievable concentrations of the agents were used for the analysis of DNA histograms and proliferation of 9L cells in vitro. Rats intracranially inoculated with 9L cells were treated with the agents, and tumor masses were visually monitored by using magnetic resonance imaging with gadolinium-diethylenetriaminepentaacetic acid enhancement. RESULTS: The cytotoxic effect of anticancer agents examined by the microtiter tetrazolium test correlated with a decreased G0/G1 peak in the DNA histograms. Serial FCM analysis showed that the decrease in the G0/G1 peak was subsequently accompanied by increased hypodiploid areas, suggesting DNA fragmentation induced by the agents. The in vitro chemosensitivity test and cell proliferation examination showed that all agents except cisplatin were effective. Growth retardation of inoculated brain tumors and prolonged survival of inoculated rats were observed with treatment with the anticancer agents, except cisplatin. CONCLUSION: The present study shows that FCM analysis with a DNA-binding dye can detect DNA damage induced by anticancer agents, and it suggests that this technique is a novel method to test chemosensitivity in vitro.

Animals↗
PubMed2002

Growth hormone downregulated the excessive apoptosis of ileal intestinal epithelial cells in rats during the early course of acute necrotizing pancreatitis.

INTRODUCTION: Growth hormone (GH) has beneficial effects in protecting the intestinal barrier integrity of rats with acute necrotizing pancreatitis (ANP), and the balance between apoptosis and proliferation of intestinal epithelium is one of the key factors in maintenance of the intestinal barrier homeostasis. AIM: To evaluate further the effect of GH on cell apoptosis of intestinal epithelium in rats with ANP. METHODOLOGY: Seventy-two rats were randomly divided into 3 groups: sham operation (SO) group (n = 24); ANP group (n = 24); and ANP with GH treatment group (n = 24). ANP in rats was established by injection of 5% sodium taurocholate into the biliopancreatic duct, and laparotomized animals without induction of ANP (sham operation) served as controls. The rats in the GH treatment group received human recombinant GH (0.75 U/kg body weight) subcutaneously once, immediately after operation. The segment of ileum was removed and the detached epithelial cells of ileum were harvested at 3 hours, 6 hours, 12 hours, and 24 hours after operation. Apoptosis of intestinal epithelium was studied by DNA gel electrophoresis, fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI) staining under flow cytometry, and the terminal deoxynucleotidyl transferase-mediated d-UTP-biotin nick end labeling (TUNEL) histochemical method. RESULTS: All specimens harvested at different time points from rats with ANP showed a marked DNA ladder pattern after agarose gel electrophoresis, in comparison with those in the SO group, indicating DNA fragmentation appeared at the early stage in the ANP group. However, a DNA ladder pattern was seen only at 3 hours after operation in the GH-treated rats. The apoptotic percentage assayed by flow cytometry with use of an annexin V kit at 6 hours in the ANP group was significantly higher than in the control group (80% +/- 9% versus 28% +/- 6%; p < 0.01) and was decreased markedly in the GH treatment group (27% +/- 15% versus 80% +/- 9%, p < 0.01). The apoptotic index, studied by the TUNEL method, was obviously higher in the ANP group than in the control group (3 hours: 18 +/- 4 versus 6 +/- 2; 6 hours: 20 +/- 3 versus 8 +/- 2; 12 hours: 15 +/- 2 versus 11 +/- 1; 24 hours: 14 +/- 2 versus 5 +/- 1; p < 0.01), whereas the apoptotic index in the GH treatment group decreased at 3 hours and 6 hours (10 +/- 2 versus 18 +/- 4; 10 +/- 2 versus 20 +/- 3; p < 0.01). The same results were achieved for the apoptotic index of villi tips in the three groups. CONCLUSION: Apoptosis is a principle model of intestinal epithelial cell death at the early stage of ANP, and GH may downregulate the apoptosis significantly. This action probably is involved in the mechanisms contributing to the protective effects of GH on intestinal barrier integrity in ANP.

Animals↗
PubMed2002

Resveratrol inhibits proliferation and induces apoptosis in human pancreatic cancer cells.

INTRODUCTION: Because of lack of early diagnosis and poor therapeutic responsiveness, median survival in patients with pancreatic cancer is <6 months, and survival beyond 5 years is rare. Thus, another dimension in chemotherapeutic agents for pancreatic cancer would be beneficial to control metastatic and unresectable disease. Resveratrol, a natural product from grapes, has been shown to be chemopreventive for carcinogen-induced skin cancer and also to inhibit proliferation of oral squamous, breast, colonic, and prostate cancer cells. AIM: To investigate the effect of resveratrol in pancreatic cancer. METHODOLOGY: To evaluate the potential role of resveratrol on pancreatic cancer cell proliferation, two human pancreatic cancer cell lines, PANC-1 and AsPC-1, were used. RESULTS: Resveratrol inhibited proliferation of both PANC-1 and AsPC-1 in a concentration- and time-dependent manner as measured by [ H]thymidine incorporation. Cell number of both PANC-1 and AsPC-1 was also significantly decreased following 48 and 72 hours of treatment with 100 micromol/L resveratrol. The growth inhibition induced by resveratrol was accompanied by apoptotic morphologic changes, characterized by cell rounding and cell membrane blebbing suggesting apoptosis. Propidium iodide staining of DNA, measured by flow cytometry, showed a dramatic increase in the fraction of sub-G0/G1 cells following resveratrol treatment in both PANC-1 and AsPC-1. The substantial apoptosis inducted by resveratrol on these two cell lines was confirmed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. CONCLUSION: These findings suggest that the natural product resveratrol may have a potent antiproliferative effect on human pancreatic cancer with induction of apoptosis. Resveratrol is likely to be valuable for the management and prevention of human pancreatic cancer.

Anticarcinogenic Agents↗