A Relationship between 5-Lipoxygenase-activating Protein and bcl-xL Expression in Murine Pro-B Lymphocytic FL5.12 Cells

Datta, Kaushik; Biswal, Shyam; Xu, Jie; Towndrow, Kelly M.; Feng, Xinwei; Kehrer, James P.

doi:10.1074/jbc.273.43.28163

Cited by 45 publications

(33 citation statements)

References 48 publications

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“…MK886 has also been shown to induce apoptosis independently of both 5-lipoxygenase and FLAP. Furthermore, induction of differentiation and apoptosis in cancer cells can also occur through the action of other oxidation products of AA (11,38,39). In this article, we focus on the effect of MK886 on PPAR induction.…”

Section: Discussionmentioning

confidence: 99%

Inhibitors of the Arachidonic Acid Pathway and Peroxisome Proliferator–Activated Receptor Ligands Have Superadditive Effects on Lung Cancer Growth Inhibition

et al. 2005

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Arachidonic acid (AA) metabolizing enzymes and peroxisome proliferator-activated receptors (PPARs) have been shown to regulate the growth of epithelial cells. We have previously reported that exposure to the 5-lipoxygenase activating protein-directed inhibitor MK886 but not the cyclooxygenase inhibitor, indomethacin, reduced growth, increased apoptosis, and up-regulated PPARA and ; expression in breast cancer cell lines. In the present study, we explore approaches to maximizing the proapoptotic effects of PPAR; on lung cancer cell lines. Non-small-cell cancer cell line A549 revealed dosedependent PPAR; reporter activity after treatment with MK886. The addition of indomethacin in combination with MK886 further increases reporter activity. We also show increased growth inhibition and up-regulation of apoptosis after exposure to MK886 alone, or in combination with indomethacin and the PPAR ligand, 15-deoxy-# 12,14 -prostaglandin J 2 compared with single drug exposures on the adenocarcinoma cell line A549 and small-cell cancer cell lines H345, N417, and H510. Real-time PCR analyses showed increased PPAR mRNA and retinoid X receptor (RXR)A mRNA expression after exposure to MK886 and indomethacin in a time-dependent fashion. The results suggest that the principal proapoptotic effect of these drugs may be mediated through the known antiproliferative effects of the PPAR;-RXR interaction. We therefore explored a three-drug approach to attempt to maximize this effect. The combination of low-dose MK886, ciglitazone, and 13-cis-retinoic acid interacted at least in a superadditive fashion to inhibit the growth of lung cancer cell lines A549 and H1299, suggesting that targeting PPAR; and AA action is a promising approach to lung cancer growth with a favorable therapeutic index. (Cancer Res 2005; 65(10): 4181-90)

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Section: Discussionmentioning

confidence: 99%

Inhibitors of the Arachidonic Acid Pathway and Peroxisome Proliferator–Activated Receptor Ligands Have Superadditive Effects on Lung Cancer Growth Inhibition

et al. 2005

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“…Interestingly, 50 M EGTA-AM, a permeant calcium chelator (31), reduced the number of apoptotic bodies induced by AEA to approximately 40 or 35% of the control, in CHP100 or U937 cells, respectively (Table II). Also 10 M ETYA or 10 M MK886, specific 5-lipoxygenase inhibitors (32,33), reduced to approximately 40 -50% the pro-apoptotic activity of AEA in both cell lines (Table II). Similar results were observed by treating the cells with 10 M indomethacin, a cyclooxygenase inhibitor (34).…”

Section: Aea-induced Pcd Is Mediated By Vanilloidmentioning

confidence: 98%

“…At variance with other types of PCD (47), calcium rise induced by AEA was not acting through activation of nitricoxide synthase, because the nitric-oxide synthase inhibitor L-NAME was ineffective in protecting cells against AEA. Instead, arachidonate degradation by 5-lipoxygenase and cyclooxygenase activities, which might be enhanced as a consequence of a rise in intracellular Ca 2ϩ (32)(33)(34), had a role in the process, because the inhibitors ETYA and MK886 significantly inhibited AEA-induced PCD (Table II). It must be mentioned that MK886 can exert lipoxygenase-unrelated effects on mammalian cells (33).…”

Section: Aea-induced Pcd Is Mediated By Vanilloidmentioning

confidence: 99%

“…Instead, arachidonate degradation by 5-lipoxygenase and cyclooxygenase activities, which might be enhanced as a consequence of a rise in intracellular Ca 2ϩ (32)(33)(34), had a role in the process, because the inhibitors ETYA and MK886 significantly inhibited AEA-induced PCD (Table II). It must be mentioned that MK886 can exert lipoxygenase-unrelated effects on mammalian cells (33). However, the observation that ETYA and MK886 yielded the same inhibition of apoptosis seems to rule out the involvement of lipoxygenase-independent pathways.…”

Section: Aea-induced Pcd Is Mediated By Vanilloidmentioning

confidence: 99%

“…However, the observation that ETYA and MK886 yielded the same inhibition of apoptosis seems to rule out the involvement of lipoxygenase-independent pathways. This seems interesting, because formation of arachidonate products unbalances the intracellular redox level and has been implicated in apoptotic death of several cell types (7,17,33,39). In particular, it should be stressed that a function for lipoxygenase in programmed organelle degradation has been recently demonstrated, showing that the enzyme can make pore-like structures in the lipid bilayer (48).…”

Section: Aea-induced Pcd Is Mediated By Vanilloidmentioning

confidence: 99%

See 2 more Smart Citations

Anandamide Induces Apoptosis in Human Cells via Vanilloid Receptors

Maccarrone

Lorenzon

Bari

et al. 2000

Journal of Biological Chemistry

327

329

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Biocompatibility of NDGA-polymerized collagen fibers. I. Evaluation of cytotoxicity with tendon fibroblastsin vitro

Koob¹,

Willis²,

Hernández³

2001

J. Biomed. Mater. Res.

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The material properties of tendon type I collagen fibers polymerized with nordihydroguaiaretic acid (NDGA) are equivalent to native tendon, suggesting that NDGA crosslinking may provide a viable approach to stabilizing collagenous materials for repairing ruptured, lacerated, or surgically transected fibrous tissues, such as tendon and ligament (Koob & Hernandez, Biomaterials, in press). Using standard cytotoxicity tests, the present study evaluated the biocompatibility of these fibers with cultured bovine tendon fibroblasts. Primary fibroblasts obtained from calf digital extensor tendons were exposed to NDGA, reaction products generated from the polymerization protocol, and the crosslinked fibers. NDGA was cytotoxic to these cells at concentrations above 100 microM. NDGA oxidation products were similarly cytotoxic. At concentrations below 100 microM, fibroblast viability was not affected by NDGA or its oxidation products. At these lower concentrations, fibroblast proliferation was unaffected compared to controls not exposed to NDGA. Fibers crosslinked with NDGA contained no unreacted NDGA, but they did contain soluble reaction products that were cytotoxic to tendon fibroblasts in both the elution and the direct contact tests. Washing the fibers in 70% ethanol and phosphate-buffered saline eliminated cytotoxicity of the fibers. Ethanol simultaneously sterilized the fibers. Tensile tests established that the ethanol/phosphate buffer wash did not adversely affect the material properties of the fibers. The results of these experiments indicate that NDGA-crosslinked fibers can be rendered nontoxic to tendon fibroblasts and may provide a novel approach for producing biologically based, biocompatible, tendon bioprostheses.

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A Relationship between 5-Lipoxygenase-activating Protein and bcl-xL Expression in Murine Pro-B Lymphocytic FL5.12 Cells

Cited by 45 publications

References 48 publications

Inhibitors of the Arachidonic Acid Pathway and Peroxisome Proliferator–Activated Receptor Ligands Have Superadditive Effects on Lung Cancer Growth Inhibition

Inhibitors of the Arachidonic Acid Pathway and Peroxisome Proliferator–Activated Receptor Ligands Have Superadditive Effects on Lung Cancer Growth Inhibition

Anandamide Induces Apoptosis in Human Cells via Vanilloid Receptors

Biocompatibility of NDGA-polymerized collagen fibers. I. Evaluation of cytotoxicity with tendon fibroblastsin vitro

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