Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.4.2.30 (PARP)
13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta1,4-Galactosyltransferase II (beta4GalT-II) is one of the enzymes transferring galactose to the terminal N-acetylglucosamine of complex-type N-glycans and its expression is significantly altered during oncogenesis with unknown functions. Here, we reported for the first time the pro-apoptotic role of beta4GalT-II in tumor cells. The level of beta4GalT-II mRNA expression was obviously decreased during HeLa cell apoptosis induced by cisplatin. Interestingly, the ectopic expression of beta4GalT-II in HeLa cells markedly increased apoptosis and cleavage of PARP induced by cisplatin as well as the expression of pro-apoptotic protein Bax. Furthermore, deletion of Golgi localization domain abolished the apoptotic role of beta4GalT-II in HeLa cells. Collectively, these results suggest that beta4GalT-II increases HeLa cell apoptosis induced by cisplatin depending on its Golgi localization, which indicates that beta4GalT-II might contribute to the therapeutic efficiency of cisplatin for cervix cancer.
...
PMID:beta4GalT-II increases cisplatin-induced apoptosis in HeLa cells depending on its Golgi localization. 1747 Mar 62

Human cervical cancer is potentially lethal, and therefore the development of effective and tolerable therapeutic options is vital. In the present study, the in vitro effect of the synthetized compound JOT01006 (C21H20C1NO4) on human cervical epithelioid carcinoma cell line (HeLa) was examined. The results demonstrated that JOT01006 induced morphological changes and cytotoxicity (decreased the percentage of viable cells) in a dose-dependent manner. JOT01006 induced apoptosis which was analyzed by flow cytometric methods and confirmed by DAPI staining and DNA fragmentation analyzed by DNA gel electrophoresis. JOT01006 also induced reactive oxygen species (ROS) overproduction before causing endoplasmic reticulum (ER) stress which was also confirmed by the increased levels of Grp78 and Gadd153. Western blotting was selected to demonstrate that JOT010006 promoted p53, Bak, PARP, caspase-3 levels and decreased the levels of Bcl-2 and Bcl-xL. Our results also showed that JOT01006 also promoted caspase-12 production followed by apoptosis. The results also showed that JOT01006 inhibited the migration of HeLa cells potentially through inhibition of MMP-2 and -9.
...
PMID:Ethyl 2- [N-m-chlorobenzyl- (2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01006) induces apoptosis in human cervical cancer HeLa cells. 1769 46

Clitocine, a natural biologically active substance isolated from the mushroom Leucopaxillus giganteus, possesses several bioactivities including antitumor. Here, for the first time, we studied the molecular mechanism of clitocine-induced apoptosis in human cervical cancer cells (HeLa). Clitocine-induced cell death was characterized with the changes in cell morphology, DNA fragmentation, activation of caspase-3, -8, and -9 (like) activities, poly(ADP-ribose) polymerase (PARP) cleavage, release of cytochrome c (cyt c) into cytosol, and increase of Bax:Bcl-2 ratio. These results indicated that the induction of apoptosis by clitocine involved the multiple pathway including death receptor and mitochondrial pathways, and strongly suggested that the mitochondrial pathways were mediated by down-regulation of Bcl-2 and up-regulation of Bax, release of cytochrome c and subsequent activation of caspase-3 followed by down stream events leading to apoptotic mode of cell death.
...
PMID:Anti-proliferative effect of clitocine from the mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells by inducing apoptosis. 1822 36

Our previous studies have shown that bee venom (BV) can induce apoptosis in human cervical cancer Ca Ski cells, but it can also affect human breast cancer cells, though its molecular mechanisms are not precisely known. In this study, the molecular mechanisms of apoptosis induced by BV in human breast cancer MCF7 cells were investigated. BV induced morphological changes (examined by phase-contrast microscopy) and inhibited the proliferation (examined by MTT assay) of MCF7 cells; both effects occurred in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species (ROS) and dysfunction of the mitochondrial membrane potential (Azm), and led to cytochrome c release, an increase in the levels of caspase-9 and Poly (ADP-ribose) polymerase (PARP) and then apoptosis. It also showed that BV induced S-phase arrest in MCF7 cells which may occur through the promotion of p53, p21, p27 and the exhibition of Cdk2. Western blotting demonstrated that BV reduced Bcl-2 and increased Bax protein levels which may have caused the changes of delta psi m. BV treatment led to ROS production up to but after treatment led to a decrease in the levels of ROS, which may be associated with the observations of BVaffecting glutathion S-transferase (GST), Zn-superoxide dismutase (Zn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase. The Comet assay also showed that BV induced DNA damage while DAPI staining also confirmed that BV induced apoptosis in examined MCF7 cells. Our results also showed that BV increased the levels of AIF and EndoG in MCF7 cells. In conclusion, our data demonstrated that BV induced apoptosis via a mitochondria-dependent pathway based on the changes of delta psi m, AIF and EndoG release in MCF7 cells.
...
PMID:The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. 1846 9

To investigate the role of poly(ADP-ribose)polymerase (PARP) in the physiological condition of cell growth, we studied the ability of PARP inhibitors to induce apoptosis. Benzamide (BA) and 4-amino-1,8-naphthalimide (NAP), two well-known inhibitors of PARP, treatment increased nuclear fragmentation and caspase-3 activity in HeLa (Human cervical cancer cell line) cells. The increase of cellular NAD(+) level was observed in HeLa cells treated with BA in comparison with untreated control cells. For unrevealing the specific PARP family member responsible for such induction of apoptosis we knocked down and over-expressed PARP-1 gene in HeLa cells. PARP-1 knock down cells were sensitive to BA induced nuclear fragmentation and caspase-3 activation while exogenous expression of PARP-1 rendered cells resistant to BA induced apoptosis. This result indicated that inhibition of PARP-1 resulted in induction of apoptosis.
...
PMID:Induction of apoptosis by the inhibitors of poly(ADP-ribose)polymerase in HeLa cells. 1869 44

Total saponin of Solanum lyratum Thunb (TSSLT), a species of natural biologically active substances isolated from Solanum lyratum Thunb, possesses various bioactivities. It has been proposed that the induction of apoptosis may be the basis of its antitumor activity. However, the molecular mechanism underlying the total saponin-induced apoptotic process remains unknown. In the present study, we describe the anti-proliferative effect of TSSLT on human cervical cancer cells (Hela). The TSSLT induced apoptosis of Hela in a time-dependent manner with an IC50 for cell viability of 6 microg/ml. The TSSLT-induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-like activities, poly (ADP-ribose) polymerase (PARP) cleavage and release of cytochrome c (cyt c) into cytosol. TSSLT activated various caspases such as caspase-3, -8, and -9 (like) activities but not caspase-1 like activity. The cell death was completely prevented by the pan caspase inhibitor benzyloxy carbonyl-Val-Ala-Asp- fluoromethyl-ketone (Z-VAD-FMK). More than 80% cell survival was observed in the presence of a caspase-3 inhibitor. In addition, treatment with TSSLT induced the increase of Bax:Bcl-2 ratio in Hela cells. These results suggest that the induction of apoptosis by TSSLT involves multiple pathways antigen including death receptor and mitochondrial pathway and strongly suggest that the mitochondrial pathway was mediated by low expression of Bcl-2 and upregulation of Bax, release of cyt c and subsequent activation of caspase-3 followed by down stream events leading to apoptotic cell death.
...
PMID:Antiproliferative activity of the total saponin of Solanum lyratum Thunb in Hela cells by inducing apoptosis. 1906 47

Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis Georgi. Here, we investigated the antitumor effect of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. We found that after inoculated with the HeLa cells the mice treated with oroxylin A showed a significant decrease of tumor volumes and tumor weight compared with the control. Meanwhile, the growth inhibition of oroxylin A on HeLa cells were observed by MTT assay and the value of IC(50) was 19.4+/-0.7 microM after treatment for 48h. Upon our previous research, the inhibition by oroxylin A might be through apoptosis. Then apoptosis induced by oroxylin A in HeLa cells was characterized by DAPI staining and Annexin V/PI double staining, and degradation of PARP (poly-ADP-ribose polymerase) was both found in HeLa cells and tumor tissue. Next, activation of the caspase cascade for both the extrinsic and intrinsic pathways were demonstrated in vivo and in vitro, including caspase-8, -9 and -3. We also found that the expression of Bcl-2 protein decreased, which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that oroxylin A exhibited strong antitumor effect in HeLa cell line and apoptosis induction involved in it.
...
PMID:Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. 1913 24

Similar to arsenic trioxide (As2O3), tetra-arsenic oxide (As4O6, TAO) has shown anti-proliferative and apoptosis-inducing effects against human leukemic and solid tumor cells. In order to assess the increase in efficacy, we evaluated the combinatory interaction of TAO combined with paclitaxel, 5-FU or cisplatin and studied its mechanism of action in the cell lines of human gastric, cervix and head and neck tumors. Two agents were combined at equitoxic ratios based on the IC50 of each drug. Efficacy improvement was evaluated using a combination index and isobologram at 50% inhibition level. Apoptosis induction and expression of apoptosis-related proteins was determined and the effect on microtubule polymerization was monitored. TAO combined with paclitaxel showed synergistic interaction in all three of gastric, cervix and head and neck cancer cell lines. On the other hand, TAO when combined with 5-FU or cisplatin showed an antagonistic interaction in head and neck or cervix cancer cell lines, respectively. Simultaneous treatment with TAO with paclitaxel resulted in an increased percentage of apoptotic cells and a significant increase in PARP cleavage and caspase-3 activation in the gastric and cervix cancer cells compared to TAO alone as well as the antagonistic groups (TAO with 5-FU or cisplatin). TAO suppressed the tubulin polymerization in the presence and absence of paclitaxel in a concentration-dependent manner, suggesting mitotic catastrophe as a potential mechanism of the synergism with paclitaxel. Overall, the present study suggests that TAO may have a greater potential as an anti-cancer agent against human gastric, cervix and head and neck tumors, in combination with paclitaxel. The synergistic interaction with paclitaxel may be associated with increased apoptosis via inhibition of paclitaxel-induced tubulin polymerization. Further detailed studies of combinatory mechanisms and evaluation using in vivo models are warranted.
...
PMID:Synergistic interaction between tetra-arsenic oxide and paclitaxel in human cancer cells in vitro. 1942 86

Naturally occurring triterpenoid compounds have long been used as anti-inflammatory, antimalarial, and insecticidal agents. It has become evident that some of the natural or synthetic triterpenoids have promising clinical potential as both a therapeutic and chemopreventive agent for cancer. However, the molecular basis for the antitumor activity of triterpenoid has yet to be defined. In this study, we show that pristimerin, a natural triterpenoid, induces mitochondrial cell death in human cervical cancer cells and that reactive oxygen species (ROS)-dependent activation of both Bax and poly(ADP-ribose) polymerase-1 (PARP-1) is critically required for the mitochondrial dysfunction. We also showed that c-Jun N-terminal kinase (JNK) is involved in ROS-dependent Bax activation. Treatment of pristimerin induced an increase in intracellular ROS, JNK activation, conformational change, and mitochondrial redistribution of Bax, mitochondrial membrane potential loss, and cell death. The PARP-1 was also found to be activated by pristimerin treatment. An antioxidant, N-acetyl-l-cysteine (NAC), inhibited pristimerin-induced JNK activation, Bax relocalization, and PARP-1 activation, as well as mitochondrial cell death. Moreover, inhibition of JNK clearly suppressed conformational change and mitochondrial translocation of Bax and subsequent mitochondrial cell death but did not affect PARP-1 activation. Inhibition of PARP-1 with 1,5-dihydroxyisoquinoline (DIQ) or with small interfering RNA of PARP-1 significantly attenuated pristimerin-induced mitochondrial membrane potential loss and cell death but did not affect JNK activation and Bax relocalization. These results indicate that the natural triterpenoid pristimerin induces mitochondrial cell death through ROS-dependent activation of both Bax and PARP-1 in human cervical cancer cells and that JNK is involved in ROS-dependent Bax activation.
...
PMID:Reactive oxygen species-dependent activation of Bax and poly(ADP-ribose) polymerase-1 is required for mitochondrial cell death induced by triterpenoid pristimerin in human cervical cancer cells. 1957 49

Lanthanides have been reported to induce apoptosis in cancer cell lines. Human cervical cancer cell line HeLa was found to be more sensitive to dicitratolanthanum (III) complex ([LaCit2](3-)) than other cancer cell lines. However, the effect and mechanism of dicitratoytterbium (III) complex ([YbCit2](3-)) on HeLa cells is unknown. Using biochemical and comparative proteomic analyses, [YbCit2](3-) was found to inhibit HeLa cell growth and induce apoptosis. Similar to the effects of [LaCit2](3-), proteomics results from [YbCit2](3-)-treated cells revealed profound changes in proteins relating to mitochondria and oxidative stress, suggesting that mitochondrial dysfunction plays a key role in [YbCit2](3-)-induced apoptosis. This was confirmed by the decreased mitochondrial transmembrane potential and the increased generation of reactive oxygen species in [YbCit2](3-)-treated cells. Western blot analysis showed that [YbCit2](3-)-induced apoptosis was accompanied by the activation of caspase-9 and specific proteolytic cleavage of PARP, leading to an increase in the pro-apoptotic protein Bax and a decrease in the anti-apoptotic protein Bcl-2. These results suggest a mitochondrial pathway of cell apoptosis in [YbCit2](3-)-treated cells, which will help us understand the molecular mechanisms of lanthanide-induced apoptosis in tumor cells.
...
PMID:A proteomic investigation into the human cervical cancer cell line HeLa treated with dicitratoytterbium (III) complex. 1963 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---