Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylation of histones and nonhistone proteins is an important post-translational modification involved in the regulation of gene expression in mammalian cells. Dysfunction of histone acetyltransferase (HAT) is often associated with the manifestation of several diseases. In this report, HATs are new targets for the development of therapeutics. Our studies first proved that curcumin induces histone hypoacetylation in brain cancer cells and finally induces apoptotic cell death through a (PARP)- and caspase 3-mediated manner. In addition, curcumin induces recontrolling of neural stem cell fates. It induces effective neurogenesis, synaptogenesis, and migration of neural progenitor cells in vitro in brain-derived adult neural stem cells. We also confirmed the neurogenic effect of curcumin in our in vivo experiments. Curcumin actively suppressed differentiation in astrocytes while promoting differentiation into the neurons associated with decrease of histone H3 and H4 acetylation. We suggest that histone hypoacetylation plays an important role in determine stem cell fate through controlling the simultaneous expression of many genes. Thus, the present finding that curcumin, a nontoxic dietary compound, is a histone acetyltransferase inhibitor would supply a new window to understand further the molecular mechanism of histone acetylase inhibitors (HAI) in cancer and neural stem cells and provide a new target molecule for treating central nervous system disorders.
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PMID:Curcumin-induced histone hypoacetylation enhances caspase-3-dependent glioma cell death and neurogenesis of neural progenitor cells. 1664 63

Curcumin (diferuloylmethane), a natural cancer chemopreventive compound, has been tested for its action in acute myeloblastic leukemia cell line HL-60. The results clearly show that curcumin induces apoptosis in these cells as evidenced by the release of cytochrome c from mitochondria to the cytosol and increase in the DNA content in sub G1 region as observed in FACS analysis. Apoptosis is apparently mediated by up-regulation of apoptotic gene bax and simultaneous down-regulation of anti-apoptotic gene bcl-2 followed by activation of caspases 3 and 8 and degradation of PARP. Telomerase, a reverse transcriptase, has been found to be activated in more than 80% of human cancers and, therefore, can be considered as a potential marker for tumorigenesis. Certain natural compounds have the potential of inhibiting telomerase activity leading to suppression of cell viability and induction of apoptosis. The present study shows that curcumin-induced apoptosis coincides with the inhibition of telomerase activity in a dose dependent manner.
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PMID:Curcumin-induced apoptosis in human leukemia cell HL-60 is associated with inhibition of telomerase activity. 1709 85

Xanthorrhizol is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhiza Roxb (Zingiberaceae). Xanthorrhizol was tested for a variety of important pharmacological activities including antioxidant and anti-inflammatory activities. An antiproliferation assay using the MTT method indicated that xanthorrhizol inhibited the proliferation of the human breast cancer cell line, MCF-7, with an EC50 value of 1.71 microg/ml. Three parameters including annexin-V binding assay, Hoechst 33258 staining and accumulation of sub-G1 population in DNA histogram confirmed the apoptosis induction in response to xanthorrhizol treatment. Western-blotting revealed down-regulation of the anti-apoptotic bcl-2 protein expression. However, xanthorrhizol did not affect the expression of the pro-apoptotic protein, bax, at a concentration of 1 microg/ml, 2.5 microg/ml and 5 microg/ml. The level of p53 was greatly increased, whilst PARP-1 was cleaved to 85 kDa subunits, following the treatment with xanthorrhizol at a dose-dependent manner. These results, thereby, suggest that xanthorrhizol has antiproliferative effects on MCF-7 cells by inducing apoptosis through the modulation of bcl-2, p53 and PARP-1 protein levels.
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PMID:Xanthorrhizol exhibits antiproliferative activity on MCF-7 breast cancer cells via apoptosis induction. 1720 Nov 74

Curcumin, a major active component of turmeric, is known to induce apoptosis in several types of cancer cells, but little is known about its activity in chemoresistant cells. Hence, the aim of the present study was to investigate the anticancer properties of curcumin in cisplatin-resistant human ovarian cancer cells in vitro. The results indicated that curcumin inhibited the proliferation of both cisplatin-resistant (CR) and sensitive (CS) human ovarian cancer cells almost equally. Enhanced superoxide generation was observed in both CR and CS cells treated with curcumin. Curcumin induced G(2)/M phase cell-cycle arrest in CR cells by enhancing the p53 phosphorylation and apoptosis through the activation of caspase-3 followed by PARP degradation. Curcumin also inhibited the phosphorylation of Akt while the phosphorylation of p38 MAPK was enhanced. In summary, our results showed that curcumin inhibits the proliferation of cisplatin-resistant ovarian cancer cells through the induction of superoxide generation, G(2)/M arrest, and apoptosis.
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PMID:Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. 1721 83

Furanodiene (C15H20O), a pure compound isolated from Traditional Chinese medicine, Curcuma wenyujin, named Ezhu in Chinese, which structure was determined on the basis of NMR, MS and UV spectrum. In this study, we attempted to characterize in detail the signaling cascades resulted from furanodiene-induced apoptosis in human hepatoma HepG2 cells. Furanodiene inhibited HepG2 cell growth by causing cell cycle arrest at G2/M and inducing apoptosis as evidenced by DNA fragmentation assay. We found that furanodiene induced mitochondrial transmembrane depolarization, release of mitochondrial cytochrome c, activation of caspases-3 and the cleavage of PARP. The furanodiene mediated mitochondria-caspase apoptotic pathway also involved activation of p38 and inhibition of ERK mitogen-activated protein kinase (MAPK) signaling. These results for the first time have identified the biological activity of furanodiene against HepG2 cells and provide rationales for further development of essential oil of Ezhu and its ingredients such as furanodiene on treatment of liver diseases.
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PMID:Furanodiene induces G2/M cell cycle arrest and apoptosis through MAPK signaling and mitochondria-caspase pathway in human hepatocellular carcinoma cells. 1761 10

Several micronutrients present in fruits and vegetables exhibit anticancer activity as a result of their actions on molecular targets involved in carcinogenesis and tumor progression. Curcumin, a phenolic phytochemical derived from the rhizome of Curcuma longa, exhibits both cancer-preventative activity and growth inhibitory effects on neoplastic cells. Several studies report that curcumin inhibits cancer cell proliferation and induces apoptosis in cancer cells through p21-mediated cell cycle arrest. Cancer cells that are deficient in p21 are also reported to be more prone to undergo apoptosis in response to a variety of cytotoxic agents. In this study, we determined whether curcumin-induced cytotoxicity in cultures of HCT-116 human colon cancer cells was dependent on p21 status. Curcumin killed wild-type HCT-116 cells in a dose- and time-dependent manner, as measured in an MTT cell viability assay. Moreover, an equivalent cytotoxic effect by curcumin was observed in both p21(+/+) and p21(-/-)HCT-116 cells, indicating that curcumin-induced cytotoxicity was p21-independent. Primary cultures of human dermal fibroblasts were less sensitive than HCT-116 colon cancer cells to lower doses of curcumin, suggesting a degree of selectivity for neoplastic cells. Western blot analysis showed that cell death in curcumin-treated cultures of p21(+/+) and p21(-/-) HCT-116 cells was associated with a reduction in pro-caspase-3 and PARP-1 cleavage, which are indicative of apoptosis. We conclude that curcumin-induced apoptosis in HCT-116 colon cancer cells does not depend on p21 status.
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PMID:Curcumin induces apoptosis in HCT-116 human colon cancer cells in a p21-independent manner. 1842 3

Furanodiene, a natural product isolated from Curcuma wenyujin, has been reported to produce cytotoxic effect. In this study, we investigated its effects on human leukemia HL60 cells. Furanodiene induced apoptosis of HL60 cells, characterized by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3, caspase-8 and caspase-9. In the Bcl-2 family proteins, Bid protein (a substrate of caspase-8) was activated by furanodiene, but Bcl-2, Bax and Bcl-xL proteins were not influenced by furanodiene stimulation. Moreover, furanodiene treatment caused the upregulation of tumor necrosis factor receptor 1 (TNFR1), the formation of TNFR1 complex and an obvious production of TNF-alpha in HL60 cells. The soluble TNFR1 receptor effectively inhibited furanodiene-induced apoptosis. Taken together, furanodiene could inhibit the growth of leukemia cells via induction of apoptosis, and TNFR1-mediated extrinsic apoptotic pathways explains furanodiene-induced apoptosis.
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PMID:Induction of apoptosis by furanodiene in HL60 leukemia cells through activation of TNFR1 signaling pathway. 1866 67

Xanthorrhizol is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhizza Roxb (Zingerberaceae). Recent studies of xanthorrhizol in cell cultures strongly support the role of xanthorrhizol as an antiproliferative agent. In our study, we tested the antiproliferative effect of xanthorrhizol using different breast cancer cell lines. The invasive breast cancer cell line, MDA-MB-231, was then selected for further investigations. Treatment with xanthorrhizol caused 50% growth inhibition on MDA-MB-231 cells at 8.67 +/- 0.79 microg/ml as determined by sulforhodamine B (SRB) assay. Hoechst 33258 nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to increase in response to xanthorrhizol treatment. Immunofluorescence staining using antibody MitoCapture and fluorescein isothiocyanate (FITC)-labeled cytochrome c revealed the possibility of altered mitochondrial transmembrane potential and the release of cytochrome c respectively. This was further confirmed by Western-blotting, where cytochrome c was showed to migrate from mitochondrial fraction to the cytosol fraction of treated MDA-MB-231 cells. Caspase activity assay showed the involvement of caspase-3 and caspase-9, but not caspase-6 or caspase-8 in MDA-MB-231 apoptotic cell death. Subsequently, cleavage of PARP-1 protein is suggested. These data suggest treatment with xanthorrhizol modulates MDA-MB-231 cell apoptosis through the mitochondria-mediated pathway subsequent to the disruption of mitochondrial transmembrane potential, release of cytochrome c, activation of caspase-3 and caspase-9, and the modulation of PARP-1 protein.
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PMID:Antiproliferative property and apoptotic effect of xanthorrhizol on MDA-MB-231 breast cancer cells. 1918 49

Curcumin, a natural compound extracted from rhizomes of curcuma Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. However, the mechanism of action of the compound remains poorly understood. In this report, we have analyzed the effects of curcumin on the cell proliferation of Burkitt's lymphoma Raji cells. The results demonstrated that curcumin could effectively inhibit the growth of Raji cells in a dose- and time-dependent manner. Further studies indicated that curcumin treatment resulted in apoptosis of cells. Biochemical analysis showed that the expression of Bax, Bid and cytochrome C were up-regulated, while the expression of oncogene c-Myc was down regulated after curcumin treatment. Furthermore, poly (ADP-ribose) polymerase (PARP) cleavage was induced by the compound. Interestingly, the antiapoptotic Bcl-2 expression was not significantly changed in Raji cells after curcumin treatment. These results suggested that the mechanism of action of curcumin was to induce mitochondrial damage and therefore led to Raji cell apoptosis. We further investigated the in vivo effects of curcumin on the growth of xenograft tumors in nude mice. The results showed that curcumin could effectively inhibit tumor growth in the xenograft mouse model. The overall results showed that curcumin could suppress the growth of Burkitt's lymphoma cells in both in vitro and in vitro systems.
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PMID:Curcumin induces apoptosis and inhibits growth of human Burkitt's lymphoma in xenograft mouse model. 1932 74

Curcumin, a yellow pigment and the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development in several types of cancer. However, its low bioavailability and potency prevent it from being effective in most chemotherapeutic applications. One potential means of circumventing this problem has been the creation of synthetic curcumin analogues. We tested the efficacy of two such analogues, known as FLLL11 and FLLL12, in human pancreatic cancer cell lines. We compared the impact of curcumin with FLLL11 and FLLL12 on cell viability in five different pancreatic cancer cell lines. Although all three compounds were capable of lowering viability in all cell lines tested, FLLL11 and FLLL12 (IC(50) values between 0.28-3.2 and 0.91-3.43 micromol/l, respectively) were substantially more potent than curcumin (IC(50) values between 8.67 and 20.35 micromol/l). In addition, FLLL11 and FLLL12 inhibited phosphorylation of signal transducer and activator of transcription 3 and AKT, two cell signaling pathways frequently found persistently active in many forms of cancer. Furthermore, FLLL11 and FLLL12 were found to be more effective than curcumin in inducing apoptosis as evidenced by increased cleavage of PARP and caspase-3 in pancreatic cancer cell lines. These results indicate that the curcumin analogues, FLLL11 and FLLL12, are more effective than curcumin in inhibiting cell viability and inducing apoptosis, and may have translational potential as chemopreventive or therapeutic agents for pancreatic cancer.
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PMID:Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells. 1938 91


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