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)

Survivin is an attractive target for tumor growth inhibition and represents a significant approach to anticancer therapy. RNA interference is an important tool for specifically down-regulating the expression of cellular genes. However, the efficiency of short hairpin RNA (shRNA) on the expression of survivin gene and the influence on the cell apoptosis transfected by the non-viral gene transfer system of ultrasound-targeted microbubble destruction was not explored. In this work, recombinant expression plasmid of shRNA targeting survivin gene was constructed and added to cultured cervical cancer cells followed by ultrasound exposure and SonoVue((R)) microbubble. Expression of survivin mRNA and protein were assessed by RT-PCR and western blot analysis. Apoptosis ratio was quantified by flow cytometry marked with annexin V and 7-AAD. After transfected for 48 h, the expression of survivin mRNA and protein were (16.67 +/- 2.73)% and (21.33 +/- 3.55)%, respectively. The apoptosis rate was (45.41 +/- 1.47)%. The differences were significant as compared with other groups (P < 0.01). In conclusion, we suggested that survivin could be regarded as an ideal anticancer target of cervical cancer. Recombinant expression plasmid of shRNA targeting survivin gene mediated by ultrasound-targeted microbubble destruction technique could effectively inhibit the expression of target gene and induce cell apoptosis. This novel method for RNA interference represents a powerful, promising non-viral technology that can be used in the tumor gene therapy and research.
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PMID:Novel ultrasound-targeted microbubble destruction mediated short hairpin RNA plasmid transfection targeting survivin inhibits gene expression and induces apoptosis of HeLa cells. 1899 Oct 17

Activated EGF receptor (EGFR) plays an oncogenic role in several human malignancies. Although the intracellular effects of EGFR are well studied, its ability to induce and modulate tumor angiogenesis is less understood. We found previously that oncogenic EGFR can be shed from cancer cells as cargo of membrane microvesicles (MVs), which can interact with surfaces of other cells. Here we report that MVs produced by human cancer cells harboring activated EGFR (A431, A549, DLD-1) can be taken up by cultured endothelial cells, in which they elicit EGFR-dependent responses, including activation of MAPK and Akt pathways. These responses can be blocked by annexin V and its homodimer, Diannexin, both of which cloak phosphatidylserine residues on the surfaces of MVs. Interestingly, the intercellular EGFR transfer is also accompanied by the onset of VEGF expression in endothelial cells and by autocrine activation of its key signaling receptor (VEGF receptor-2). In A431 human tumor xenografts in mice, angiogenic endothelial cells stain positively for human EGFR and phospho-EGFR, while treatment with Diannexin leads to a reduction of tumor growth rate and microvascular density. Thus, we propose that oncogene-containing tumor cell-derived MVs could act as a unique form of angiogenesis-modulating stimuli and are capable of switching endothelial cells to act in an autocrine mode.
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PMID:Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. 1923 31

Macranthoside B (MB) is a hederagenin saponin extracted from the flower bud of Lonicera macranthoides. In this study, we defined the anticancer effect of MB both in vitro and in vivo using cell proliferation assays and xenograft tumor growth assays. Our data indicate that MB inhibits the proliferation of various kinds of cancer cells with IC(50) values in the range of 10-20 microM. Moreover, the volume and weight of xenograft tumors in nude mice treated with 5mg/kgMB were decreased remarkably compared to those of the vehicle control group. Furthermore, DAPI staining and flow cytometry analysis with Annexin V/PI double staining revealed that more apoptotic cells were observed following MB treatment. In addition, degradation of PARP (poly-ADP-ribose polymerase), and activation of the caspase cascade for intrinsic pathways were observed. We also found that the expression of Bcl-2 protein decreased and the protein level of Bax increased which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that MB exhibited strong anti-tumor effect and mitochondrion-mediated apoptosis induction involved in it.
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PMID:Macranthoside B, a hederagenin saponin extracted from Lonicera macranthoides and its anti-tumor activities in vitro and in vivo. 1940 96

The non-steroidal anti-inflammatory drug tolfenamic acid (TA) inhibits proliferation of SEG-1 and BIC-1 esophageal cancer cells with half-maximal growth inhibitory concentration values of 36 and 48 muM, respectively. TA also increased Annexin V staining in both cell lines, indicative of proapoptotic activity. Treatment of SEG-1 and BIC-1 cells with TA for up to 72 h decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and this was accompanied by decreased expression of the well-characterized Sp-regulated genes cyclin D1, vascular endothelial growth factor and survivin. TA also decreased hepatocyte growth factor receptor, (c-Met), a receptor tyrosine kinase that is overexpressed in esophageal cancer cells and tumors and is an important drug target. Knockdown of Sp1, Sp3 and Sp4 by RNA interference in SEG-1 and BIC-1 cells also decreased c-Met expression, demonstrating that c-Met is an Sp-regulated gene in esophageal cancer cells. Sp1 was overexpressed in esophageal cancer cells and tumors and increased Sp1 staining was observed in esophageal tumors from patients. TA (20 mg/kg/day) also decreased tumor growth and weight in athymic nude mice bearing SEG-1 cells as xenografts and this was accompanied by increased apoptosis and decreased Sp1 and c-Met staining in tumors from treated mice. Thus, TA-dependent downregulation of Sp transcription factors and c-Met defines a novel chemotherapeutic approach for treatment of esophageal cancer.
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PMID:Tolfenamic acid inhibits esophageal cancer through repression of specificity proteins and c-Met. 1940 33

Berbamine, a natural compound from the plant Berberis amurensis, is a traditional Chinese medicine mainly used in stimulating normal hematopoiesis in clinic. Our previous studies demonstrated that berbamine has anti-leukemia activity. In this study, we investigated the anticancer activity of berbamine against human hepatocellular carcinoma (HCC) HepG2 cells in vitro and in vivo. Berbamine treatment decreased the cell growth in a dose-dependent manner with an IC(50) value of 34.5 +/- 0.5 microM. Flow cytometric analysis of apoptosis using Annexin V/propidium iodide staining showed that the percentage of apoptotic cells was increased in a time-dependent manner. Berbamine treatment increased the expression level of Fas and P53, caused depolarization of mitochondrial membrane and decrease of membrane potential, and activated caspase-3, -8, and -9 in HepG2 cells. Berbamine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk. HepG2 human HCC xenograft mice treated with berbamine showed a significant reduction in tumor growth rates compared to saline-treated mice. These studies suggest that berbamine exerts anticancer effects on human HCC HepG2 cells in vivo and in vitro, the induction of p53 and the activity of the Fas apoptotic system may participate in the anticancer activity of berbamine in HepG2 cells.
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PMID:Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice. 1940 45

To investigate the mechanism of enhancing apoptosis-inducing effects of 5-fluorouracil on human colorectal adenocarcinoma cells by stable transfection of extrinsic Fas-associated death domain protein (FADD) gene, both in vitro and in vivo. FADD gene of stable overexpression was determined by reverse transcription polymerase chain reaction (RT-PCR) assay and Western blotting assay. After treatment with 5-fluorouracil as an apoptotic inducer, in vitro cell growth activities were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis and its rates were evaluated by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and flow cytometry of annexin V-FITC/PI staining. To examine the combination therapeutic effect of FADD and 5-fluorouracil, tumor xenograft model was prepared for in vivo study. Compared with SW480 and SW480/neo cells, FADD mRNA and protein levels of SW480/FADD cells were higher. Chemosensitivity and apoptosis rates of SW480/FADD cells were remarkably higher than SW480 and SW480/neo cells when treated with 5-fluorouracil. In in vivo study, overexpression of FADD increased the efficacy of 5-fluorouracil-induced inhibition of tumor growth in nude mice. Stable overexpression of extrinsic FADD gene can conspicuously ameliorate apoptosis-inducing effects of 5-fluorouracil on colorectal adenocarcinoma cells, which is a novel strategy to improve chemotherapeutic effects on colorectal cancer.
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PMID:Overexpression of FADD enhances 5-fluorouracil-induced apoptosis in colorectal adenocarcinoma cells. 1941 36

Interleukin-12 (IL-12) is effective in treating many types of rodent tumors, but has been unsuccessful in most human clinical trials, suggesting that animal models of more clinical relevance are required for evaluating human cancer immunotherapy. Herein, we report on the effectiveness of gene therapy with plasmid encoding human IL-12 (pIL-12) through in vivo electroporation in the treatment of beagles with a canine tumor, the canine transmissible venereal tumor (CTVT). The optimal electroporation conditions for gene transfer into CTVTs were tested by luciferase activity and determined to be a voltage of 200 V and duration of 50 msec, with the number of shocks set at 10 pulses, and the use of an electrode with 2 needles. Under these conditions, intratumoral administration of as little as 0.1 mg pIL-12 followed by electroporation significantly inhibited the growth of well-established tumors and eventually led to complete tumor regression. Furthermore, local pIL-12 treatment also induced a strong systemic effect that prevented new tumor growth and cured established tumors at distant locations. Intratumoral administration of pIL-12 greatly elevated the IL-12 level in the tumor masses, but produced only a trace amount in the serum. A high level of IFN-gamma mRNA was also detected in the treated tumor masses. pIL-12 gene therapy attracted significantly more lymphocytes infiltrating the tumors, including CD4(+) and CD8(+) T cells, and the surface expression of MHC I and MHC II molecules on CTVT cells was greatly increased after pIL-12 therapy. This treatment also induced apoptosis of the tumor cells as detected by Annexin V. More importantly, delivery of pIL-12 with intratumoral electroporation did not result in any detectable toxicity in the dogs. We conclude that intratumoral electroporation of the pIL-12 gene could cause profound immunologic host responses and efficiently treat CTVT in beagle dogs. The results also indicate that CTVT is an excellent large animal cancer model for testing immunogene therapies mediated by electroporation.
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PMID:Electroporation-mediated IL-12 gene therapy in a transplantable canine cancer model. 1943 Nov 45

Melanoma is one of the most chemo-resistant cancers. The remission rate of current therapy remains low. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a group of antitumor antibiotics that binds to N2 of guanine to form a DNA adduct. However, significant cardiotoxicity hampers their clinical use. We have previously synthesized a PBD indole conjugate (IN6CPBD) that induced apoptosis in several cancer cell lines. The purpose of this study was to assess the efficacy and safety of the IN6CPBD for established murine melanoma cells in vivo. IN6CPBD induced more apoptosis than DC-81 as evidenced by sub-G1 distribution, annexin V positivity, and decrease mitochondrial membrane potential (DeltaPsi(mt)). The melanomas were established in C57BL/6 mice by injecting B16F10 cells via the tail vein. Three courses of therapy were instituted after day 5 and the mice were sacrificed at day 20. The tumor growth rate in the foot pad was significantly reduced in IN6CPBD-treated mice than that in DC-81- and PBS-treated mice. The tumor burden in the lungs was also reduced significantly in IN6CPBD-treated mice accompanied with the most prominent TUNEL staining. Renal function, and cardiac enzymes were not altered significantly by IN6CPBD or DC-81, however, robust deterioration of liver function was noticed in the DC-81-treated mice. In summary, potent apoptosis could be elicited by the PBD indole conjugate IN6CPBD, accompanied with a better efficacy and less liver function impairment than the mother compound DC-81 in treating established melanoma metastasis in vivo.
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PMID:Pyrrolo[2,1-c][1,4]benzodiazepine and indole conjugate (IN6CPBD) has better efficacy and superior safety than the mother compound DC-81 in suppressing the growth of established melanoma in vivo. 1943 78

LYG-202 is a newly synthesized flavonoid with a piperazine substitution. We investigated the antitumor effect of LYG-202 in vivo and in vitro. We show that, LYG-202 significantly decreases tumor growth in mice inoculated with S180 sarcoma cells, compared with the control group. Meanwhile, the viabilities of various kinds of tumor cells were inhibited by LYG-202 with IC(50) values in the range of 4.80 to 27.70 microM. Then apoptosis induced by LYG-202 in HepG2 cells was characterized by DAPI staining and Annexin V/PI double staining and degradation of PARP was observed. Activation of the caspase cascade for both the extrinsic and intrinsic pathways was demonstrated, including caspase-8, -9, and -3. The results also showed that the expression of Bcl-2 protein decreased whereas that of Bax protein increased, leading to an increase of the Bax/Bcl-2 ratio. Our results demonstrated that LYG-202 exhibited strong antitumor effect in vivo and in vitro, involving with apoptosis induction.
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PMID:LYG-202, a new flavonoid with a piperazine substitution, shows antitumor effects in vivo and in vitro. 1948 Oct 59

The purpose of this study is to investigate the efficacy and the mechanism of Hsp90 inhibition of Withaferin A (WA), a steroidal lactone occurring in Withania somnifera, in pancreatic cancer in vitro and in vivo. Withaferin A exhibited potent antiproliferative activity against pancreatic cancer cells in vitro (with IC(50)s of 1.24, 2.93 and 2.78 microM) in pancreatic cancer cell lines Panc-1, MiaPaCa2 and BxPc3, respectively. Annexin V staining showed that WA induced significant apoptosis in Panc-1 cells in a dose-dependent manner. Western blotting demonstrated that WA inhibited Hsp90 chaperone activity to induce degradation of Hsp90 client proteins (Akt, Cdk4 and glucocorticoid receptor), which was reversed by the proteasomal inhibitor, MG132. WA-biotin pull down assay of Hsp90 using Panc-1 cancer cell lysates and purified Hsp90 showed that WA-biotin binds to C-terminus of Hsp90 which was competitively blocked by unlabeled WA. Co-immunoprecipitation exhibited that WA (10 microM) disrupted Hsp90-Cdc37 complexes from 1 to 24h post-treatment, while it neither blocked ATP binding to Hsp90, nor changed Hsp90-P23 association. WA (3, 6mg/kg) inhibited tumor growth in pancreatic Panc-1 xenografts by 30% and 58%, respectively. These data demonstrate that Withaferin A binds Hsp90, inhibits Hsp90 chaperone activity through an ATP-independent mechanism, results in Hsp90 client protein degradation, and exhibits in vivo anticancer activity against pancreatic cancer.
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PMID:Withaferin A targets heat shock protein 90 in pancreatic cancer cells. 1976 45


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