Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracts of Hypericum perforatum (St. John's wort) are widely and effectively used in the treatment of mild to moderate depression. In addition, hypericin, a component of Hypericum p. extracts, exhibits light-dependent phototoxic properties and can be used in phototherapy. We therefore investigated the cytotoxic activity of two total Hypericum p. extracts, namely from fresh and dried plants in the dark and after exposure to 7.5 J/cm2 white light illumination and compared it with the effect of hypericin on K562, U937, LN229 glioblastoma cell lines and normal human astrocytes. The chemical toxicity of non-illuminated Hypericum p. extracts in the cells tested is low as expressed by a LC50 between 1.9-4.1 mg/ml, which corresponds to 10.3-17.3 microM hypericin and 114.4-190.7 microM hyperforin after 48 h treatment. Hypericum p. extracts induced dose-dependent growth arrest of human malignant cells in the absence of illumination with GI50 values between 0.43-1.77 mg/ml (2.3-9.7 microM hypericin, 26.1-106.7 microM hyperforin) for the fresh plant extract and 0.59-3.03 mg/ml (2.5-12.8 microM hypericin, 24.2-124.7 microM hyperforin) for the dried extract. The growth inhibitory effect of fresh Hypericum p. extract was more pronounced in leukemia cell lines K562 and U937, the GI50 concentrations being about 7-fold lower than the corresponding LC50 for the cell lines K562 and U937, but almost the same as the LC50 for LN229 and NHA cells. GI50 (microgram/ml) for tumor cell lines K562 and U937 (432 and 799) established after 48 h differed significantly (p < 0.05) from those of LN229 and normal human astrocytes (1767 and 2900). The light-exposed extracts were more toxic, their LC50 and GI50 values were reduced to values corresponding to LC50 concentration of 3.7-7.4 microM and a GI50 of 1.3-3.5 microM for phototoxic hypericin. After exposure to light, there was a significant difference (p = 0.006) between the GI50 of glioblastoma LN229 cells (582 micrograms/ml) and normal human astrocytes (1050 micrograms/ml). Morphological examination by light microscopy and phosphaditylserine exposure on the outer plasma membrane investigated by Annexin V-binding with flow cytometry after 24 h confirmed that Hypericum p. extracts caused apoptosis of treated cells without exposure to light. Hypericum p. extracts derived from fresh herbs and from dried herbs which differ in their levels of phloroglucinols (hyperforin and adhyperforin) were compared. The hyperforin content of fresh St. John's wort extract exceeded that of dried plant extract by 47% and the GI50 values of fresh plant extract were 73%, 77% and 58% of those established for dried extract in the three malignant cell lines K562, U937 and LN229 in the dark (p < 0.05). Under white light (7.5 J/cm2), both extracts exerted comparable growth inhibitory and apoptosis inducing effects due to the phototoxicity of hypericin, the corresponding concentrations of which were in the range of 1.3-3.5 microM. The data reported in this study suggest that illumination is not essential for the growth inhibitory and apoptotic effects of Hypericum p. extracts, but light activation potentiates them. Furthermore, the constituent hyperforin is at least partly responsible for these effects in the dark.
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PMID:Aqueous ethanolic extract of St. John's wort (Hypericum perforatum L.) induces growth inhibition and apoptosis in human malignant cells in vitro. 1206 Dec 57

Apoptosis, a genetically encoded process of cellular suicide, comprises an intrinsic cellular defence against tumorigenesis. bak(for bcl-2 homologous antagonist/killer) is a new apoptosis-inducing gene found recently, which is identified in all tissues examined. Initial work of Farrow, Chittenden and Klefer indicated that bak plays an important role in apoptosis. Successive work of others suggests inactivity of Bak always accompanies the development of tumor cells. In this work, a shuttle vector harboring bak gene, pCA13-bak, was constructed and used to cotransfect into the cell line 293 together with a recombinant plasmid, pBHG11, containing most of adenovirus genome. A mutant adenovirus(delete E1, E3 region)carring bak, Ad-bak, was obtained, and purified. Dot blot identified the construction of recombinant virus was successful. HeLa cells were infected by this virus. Some manners were used to identify the changes of HeLa cells including Annexin V-FITC staining which made the reversed PS observed directly, microscope observation and others. The characteristic morphology of apoptotic cells was due to Ad-bak. The experiment suggests that bak is a strong apoptosis-inducing gene, and a potential gene which could be used in gene therapy on tumor.
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PMID:Induction of Apoptosis in Tumor Cells by a Recombinant Adenovirus with bak Gene. 1207 28

Ganoderma lucidum has been widely used as a remedy to promote health and longevity in China. The polysaccharide component with a branched (1-->3)-beta-D-glucan moiety from G. lucidum (PS-G) has shown evidence of enhancement of immune responses and of eliciting anti-tumor effects. In this study, we investigated the effect of PS-G on neutrophil viability, which is manifested by spontaneous apoptosis. Annexin V staining and MTT assays reveal that PS-G is able to inhibit spontaneous and Fas-induced neutrophil apoptosis, and this effect of PS-G is enhanced by the presence of zVAD (a caspase inhibitor) and GM-CSF. The antiapoptotic effect of PS-G is diminished by the presence of wortmannin and LY294002 (two PI-3K inhibitors), but is not altered by PD98059 (a MEK inhibitor). Western blotting indicates the stimulating effect of PS-G on Akt phosphorylation and its inhibition of procaspase 3 degradation, which occurs in neutrophils undergoing spontaneous apoptosis or triggered death by Fas. Taken together, PS-G elicitation of antiapoptotic effects on neutrophils primarily relies on activation of Akt-regulated signaling pathways.
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PMID:Polysaccharide purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway. 1210 Dec 82

Lovastatin, a drug successfully used in the clinic to prevent and to treat coronary heart disease, has recently been reported to decrease the incidence of melanoma in lovastatin-treated patients. Lovastatin has also been proved to potentiate antitumor effects of both cisplatin and TNF-alpha in murine melanoma models. Recently, an augmented therapeutic effect of lovastatin and doxorubicin has been reported in 3 tumor models in mice. In our preliminary study lovastatin caused retardation of melanoma growth in mice treated with doxorubicin (Feleszko et al. J Natl Cancer Inst 1998;90:247-8). In the present report, we supplement our preliminary observations and demonstrate in 2 murine and 2 human melanoma cell lines that lovastatin effectively potentiates the cytostatic/cytotoxic activity of doxorubicin in vitro via an augmentation of apoptosis (estimated with PARP-cleavage assay, annexin V assay and TUNEL). The combined antiproliferative activity of lovastatin and doxorubicin was evaluated using the combination index (CI) method of Chou and Talalay, revealing synergistic interactions in melanoma cells exposed to lovastatin and doxorubicin. In B16F10 murine melanoma model in vivo, we have demonstrated significantly increased sensitivity to the combined treatment with both lovastatin (5 mg/kg for 14 days) and doxorubicin (4 x 1 mg/kg) as compared with either agent acting alone. Lovastatin treatment resulted also in significant reduction of the number of experimental metastasis in doxorubicin-treated mice. The results of our studies suggest that lovastatin may enhance the effectiveness of chemotherapeutic agents in the treatment of malignant melanomas.
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PMID:Lovastatin potentiates antitumor activity of doxorubicin in murine melanoma via an apoptosis-dependent mechanism. 1211 96

Hemsleya amabilis extract is derived from the medicinal herb Hemsleya amabilis, which has long been used to treat cancer and many other conditions. The underlying mechanism is not clear. To investigate Hemsleya amabili's anticancer activity, we have treated different types of cancer cells including human astrocytoma U87 cells, breast cancer cells MDA-MB-231and Jurkat cells with Hemsleya amabilis extract. This agent significantly inhibited tumor cell growth and colony formation at various concentrations. When astrocytoma cells were seeded in the presence of Hemsleya amabilis extract at very low concentrations, cell spreading was greatly inhibited. Hemsleya amabilis extract also promoted tumor cell death in all the tested cell lines, but with varied sensitivities. Apoptotic assays with Annexin V staining demonstrated that Hemsleya amabilis extract induced astrocytoma cell apoptosis at different concentrations.
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PMID:Anticancer activity of Hemsleya amabilis extract. 1220 74

Ras-homologous GTPases are involved in the regulation of genotoxic stress-induced gene expression and cell death. Since they need C-terminal isoprenylation for correct intracellular localization and function, we investigated whether depletion of cells from isopren precursor moieties using the HMG-CoA reductase inhibitor lovastatin affects cellular sensitivity to DNA damaging drugs. Here we show that lovastatin renders cells highly resistant to the tumor-therapeutic compound doxorubicin. Desensitization by lovastatin was reverted by co-treatment with GGPP indicating that inhibition of protein geranylgeranylation is involved in acquired doxorubicin resistance. Lovastatin does not influence cellular sensitivity to DNA damaging compounds such as cisplatin, methyl methanesulfonate and ionizing radiation. The frequency of apoptotic cell death induced by doxorubicin was not affected by lovastatin as shown by both annexin V and DNA fragmentation assay. However, lovastatin releases cells from doxorubicin induced G2 blockage. Furthermore, lovastatin protects cells from doxorubicin-induced DNA strand breakage without affecting drug uptake or the expression of multidrug resistance protein (mdr-1). Since lovastatin confers cross-resistance to the topoisomerase II specific inhibitor etoposide, we suggest desensitization by the statin to be related to topoisomerase II function. The finding that lovastatin renders cells resistant to doxorubicin and etoposide by reducing their genotoxic and cytotoxic effects might have clinical implications for cancer therapy.
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PMID:The HMG-CoA reductase inhibitor lovastatin protects cells from the antineoplastic drugs doxorubicin and etoposide. 1223 96

We have recently described a novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437/AHPN) that induces apoptosis in a number of malignant cell types. We now describe our studies examining the effects of CD437 and a nonretinoidal analog (MM002) on the in vitro proliferation of the ALL-REH cell line, the in vitro and in vivo growth of a novel Epstein-Barr virus-negative (EBV(-)) B-cell chronic lymphocytic leukemia (B-CLL) cell line (WSU-CLL), and primary cultures of human B-CLL and acute lymphoblastic leukemia (ALL) cells. CD437 and MM002 induce apoptosis in both cell lines, as indicated by the activation of caspase-2 and caspase-3, cleavage of poly(adenosine diphosphate-ribose) (poly(ADP-ribose)) polymerase, increase in annexin V binding, and subsequent nuclear fragmentation. CD437-mediated apoptosis was not associated with the modulation of Bcl-2, Bax, or Mcl-1 levels, but was associated with the cleavage of the antiapoptotic protein Bcl-X(L) to a proapoptotic 18-kD form. This cleavage of Bcl-X(L) was dependent on caspase-3 activation since Bcl-X(L) cleavage and apoptosis were inhibited by the caspase-3 inhibitor Z-DVED-fmk. CD437 markedly inhibited the growth of WSU-CLL cells in severe combined immunodeficiency (SCID) mice. Tumor growth inhibition, growth delay, and log cell kill were 85.7%, 21 days, and 2.1, respectively, in the treated mice. Moreover, 1 of the 5 treated mice was tumor-free longer than 150 days and thus was considered cured. Exposure of primary cultures of both B-CLL and ALL cells obtained from patients to CD437 and MM002 resulted in their apoptosis. These results suggest that CD437 and MM002 analogs may have a potential role in the treatment of B-CLL and ALL.
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PMID:Induction of apoptosis of human B-CLL and ALL cells by a novel retinoid and its nonretinoidal analog. 1235 3

The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC(50) concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G(1) peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodide- and annexin V-stained cells indicated that the growth-inhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased (13)C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC(50) (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects.
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PMID:Fermented wheat germ extract inhibits glycolysis/pentose cycle enzymes and induces apoptosis through poly(ADP-ribose) polymerase activation in Jurkat T-cell leukemia tumor cells. 1235 27

It has been reported that overexpression of wild-type p53 protein induces suppression of tumor cell growth in vivo and in vitro. In this study, we further evaluated the differential effects of p53 delivered in an adenovirus vector on the cell growth, apoptosis and cell cycle progression in cervical cancer cell lines. We constructed a recombinant adenovirus expressing p53 and then delivered this into cervical carcinoma cell lines (CaSki, SiHa, and HeLa, HeLaS3) along with adenovirus expressing beta-galactosidase as a negative control. Adenovirus-delivered p53 overexpression resulted in a more significant suppression of cell growth in HPV 18-infected cells (HeLa and HeLaS3) and a lesser suppression in HPV 16-infected cells (CaSki and SiHa). However, no suppression was observed in cells infected with a negative control virus. p53 overexpression also induced apoptosis and cell cycle arrest, as determined by annexin V and propidium iodide staining. In particular, the cell cycle was arrested in the G(2)/M phase in CaSki cells. In contrast, cell cycles were arrested in the G(1) phase in HeLa cells, suggesting that the arrest phase is dependent upon the cervical cancer cell line. Taken together, these data support the idea that overexpressed p53 protein plays a differential role in suppressing cervical cancer cell growth through apoptosis and cell cycle arrest in either G(1) or G(2)/M phase, depending on the cancer cell line.
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PMID:Differential suppression of human cervical cancer cell growth by adenovirus delivery of p53 in vitro: arrest phase of cell cycle is dependent on cell line. 1235 55

Ganglioside-induced apoptosis in the cells of IL-2-dependent cytotoxic murine cell line CTLL-2 was shown to be caspase dependent: GM1-, GM2-, and GD3-induced suppression of cell proliferation was cancelled by a general caspase inhibitor Z-VAD-FMK. Ganglioside-induced apoptosis pathways are different for different individual glycolipids; the differences exist both at the initiation and effector stages of the caspase cascade. Only for GM1-induced process, molecular mechanisms of signal transduction coincide with the ones for CD95 and TNFalpha: the participation of both the main initiation caspases 8, 1, and 4, and caspases 3 and 9 as well, has been shown. Caspase 3 participates in the pathway induced by GM3, GD1a, GD1b, and GT1b, but not by GM2. As morphological features show, tumor-associated ganglioside GM2 is also a stimulus of programmed cell death (PCD) for CTLL-2 cell line: addition of GM2 into cell culture has resulted in appearance of annexin V-positive cells and in accumulation of DNA breaks (shown by the TUNEL direct dyeing of the open ends). But a caspase 3 inhibitor Z-DEVD-FMK did not restore the cell proliferation suppressed by GM2, and addition of a fluorescent substrate of caspase 3 Ac-DEVD-AFC did not result in the fluorescence development. So caspase 3 does not participate in downstream pathways of GM2-induced cell apoptosis, and a PCD-effector system other than the apoptosome-mediated one is involved here.
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PMID:Influence of gangliosides on the IL-2- and IL-4-dependent cell proliferation. 1237 11


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