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

Naringenin (NGEN), one of the most abundant flavonoids in citrus fruits, has been shown to inhibit in vitro growth of in human cancer cells, although the mechanism of action is poorly understood. Herein, we investigated NEGN's pro-apoptotic effect on human leukemia THP-1 cells. NGEN treatment inhibited THP-1 cells' growth a concentration-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies and the accumulation of cells in the sub-G1 phase. NGEN-induced apoptosis was accompanied by increased hyperpolarization of the mitochondrial membrane potential, downregulation of Bcl-2, upregulation of Bax, activation of caspases and subsequent poly(ADP-ribose)polymerase (PARP) cleavages. z-DEVD-fmk, a caspase-3 inhibitor, significantly inhibited both the cytotoxic effect and apoptotic characteristics induced by NGEN treatment demonstrating caspase-3's important role in the observed cytotoxic effect. The induction of apoptosis was also associated with the inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt, and PI3K inhibitor LY29004 significantly increases NGEN-induced cell death. These findings provide evidence that NEGN's pro-apoptotic effect is mediated by the activation of caspases and mitochondria dysfunctions that correlate with the inactivation of the PI3K/Akt pathway in THP-1 cells. Therefore, NGEN has a strong potential as a therapeutic agent for preventing cancers such as leukemia.
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PMID:Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells. 1893 Jul 80

Naringenin, a flavonoid in grapefruits and citrus fruits, has been reported to exhibit anti-inflammatory and anti-oxidative activities. Contact hypersensitivity (CHS) is a T cell-mediated immune reaction, and the factors released from macrophages also contribute to this response. Previous studies showed that naringenin suppressed CHS by inhibiting activation and migration of macrophages. However, little is known about naringenin's effects on T lymphocytes. Our study indicated that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment. Furthermore, naringenin reduced CD69 (the protein level) and cytokines such as IL-2, TNF-alpha, and IFN-gamma (the mRNA level) expressions which highly expressed by activated T cells. Meanwhile, naringenin also induced T cell apoptosis by upregulation of Bax, Bad, PARP, cleaved-caspase 3 and downregulation of phosphorylated Akt, Bcl-2. These findings suggest that, besides its anti-inflammatory activities in macrophages, naringenin also showed inhibitory effects on the activation and proliferation of T cells to alleviate symptoms of contact hypersensitivity.
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PMID:A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression. 2047 63

Naringenin (NAR) as one of the flavonoidsobserved in grapefruit has been reported to exhibit an anti-cancer activity. Activating transcription factor 3 (ATF3) is associated with apoptosis in human colon cancer cells. This study was performed to investigate the molecular mechanism by which NAR stimulates ATF3 expression and apoptosis in human colon cancer cells. NAR reduced the cell viability and induced an apoptosis in human colon cancer cells. ATF3 overexpression increased NAR-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by NAR. NAR increased ATF3 expression in both protein and mRNA level, and increased the luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by NAR is located between -317 and -148 of ATF3 promoter. p38 inhibition blocked NAR-mediated ATF3 expression, its promoter activation and apoptosis. The results suggest that NAR induces apoptosis through p38-dependent ATF3 activation in human colon cancer cells.
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PMID:Naringenin-Mediated ATF3 Expression Contributes to Apoptosis in Human Colon Cancer. 2679 11

Malignant melanoma is one of the most deadly skin cancer, due to its aggressive proliferation and metastasis. Naringenin, abundantly present in citrus fruits, has widely studied in cancer therapy. In this study, we investigated whether naringenin also has anticancer effects against B16F10 murine and SK-MEL-28 human melanoma cells. Moreover, we assessed the effects of naringenin treatment on angiogenesis of HUVECs and ex vivo sprouting of microvessels.Naringenin inhibited tumor cell proliferation and migration in a dose-dependent manner in B16F10 and SK-MEL-28 cells, which is supported by the results that phosphorylation of ERK1/2 and JNK MAPK decreased. Furthermore, naringenin induced cell apoptosis. Western blot analysisshowed naringenin treatment significantly upregulated the protein expression of activated cas3 and PARP in B16F10 and SK-MEL-28 cells. In addition, in vitro and ex vivo angiogenesis assays demonstrated that naringenin treatment potently suppressed EC migration, tube formation, and sprouting of microvessels. RT-PCR analysis showed that naringenin treatment significantly reduced the mRNA expression of Tie2, but did not inhibit the expression of Ang2. In conclusion, present study demonstrates the anticancer effects of naringenin by its induction of tumor cell death and inhibition of angiogenesis in malignant melanoma, suggesting that naringenin has potential as a safe and effective therapeutic agent to treat melanoma.
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PMID:Naringenin exerts anticancer effects by inducing tumor cell death and inhibiting angiogenesis in malignant melanoma. 3317 25