Lipoxygenase Pathway of Arachidonic Acid Metabolism in Growth Control of Tumor Cells of Different Type

Kudryavtsev, I. A.; Гудкова, М. В.; Павлова, О. М.; Oreshkin, A. E.; Myasishcheva, N. V.

doi:10.1007/s10541-005-0275-0

Cited by 12 publications

(13 citation statements)

References 27 publications

(30 reference statements)

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“…Further, specific 12‐LOX inhibitor, baicalein, and COX‐2 inhibitor, celecoxib, alone or in combination, effectively suppressed the growth of A431 cells and significantly lowered the incorporation of thymidine into DNA. The addition of exogenous 12‐(S)‐HETE, on the other hand, increased the incorporation of thymidine into DNA in a dose‐dependent manner which was in accordance with the earlier report (19). A similar increase in the proliferation of prostate (20) and gastric cancer cells (21) was reported in response to 12‐(S)‐HETE.…”

Section: Discussionsupporting

confidence: 92%

“…Most tumor cells produce AA metabolites and these compounds have been found to modulate a wide range of biological factors that induce growth and invasiveness of tumors (7). Recent investigations have shown that tumors of different histogenesis differ considerably in the metabolism of AA (19). Consequently, the expression and role of the AA metabolizing enzymes would be different in different cancers, thus necessitating an understanding of the expression profile of AA metabolizing enzymes.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of 12‐LOX and COX‐2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K‐Akt signalling pathways

Agarwal

Achari

Praveen

et al. 2009

Experimental Dermatology

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Eicosanoids, the oxygenated metabolites of arachidonic acid (AA), mediate a variety of human diseases, such as cancer, inflammation and arthritis. To evaluate the role of eicosanoids in epidermoid carcinoma, the expression of AA metabolizing enzymes, such as lipoxygenases (LOXs) and cyclooxygenases (COXs), was analysed in a human epidermoid carcinoma cell line (A431). These studies revealed overexpression of 12-R-LOX and COX-2 in A431 cells. Baicalein (a 12-LOX inhibitor) and celecoxib (a COX-2 inhibitor) significantly reduced thymidine incorporation, whereas 12-(R)-HETE and 12-(S)-HETE (12-LOX metabolites) and PGE(2) (COX-2 metabolite) significantly enhanced thymidine incorporation, suggesting a role for these enzymes in the regulation of A431 cell proliferation. Further studies on the mechanism of cell death by baicalein and celecoxib revealed that the induction of apoptosis in A431 cells was associated with reduction in the Bcl-2/Bax ratio, release of cytochrome c, activation of caspase-3 and PARP cleavage. The apoptosis induced by baicalein and celecoxib was mediated by down regulation of ERK and PI3K-Akt pathways. Further, 12-(R)-HETE, 12-(S)-HETE and PGE(2) upregulated the p-ERK and p-Akt levels, suggesting the involvement of ERK and Akt pathways in the 12-LOX- and COX-2-mediated regulation of growth in A431 cells. Our findings suggest that 12-R-LOX and COX-2 play a critical role in the regulation of growth in epidermoid carcinoma and that their inhibitors may be of potential therapeutic importance.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Inhibition of 12‐LOX and COX‐2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K‐Akt signalling pathways

Agarwal

Achari

Praveen

et al. 2009

Experimental Dermatology

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“…Resting A549 lung [30] and Caco-2 colon [31] cancer cells likewise localize cPLA 2 α to internal membranes. Since PC3, MDA-MB-231, A549, and Caco-2 cells overproduce eicosanoids or platelet-activating factor and use these products to promote their own growth [27,[32][33][34][35], constitutive localization of cPLA 2α to membranes may underlie the over-production of PL-derived mediators and thereby certain aspects of the malignant phenotype.…”

Section: Discussionmentioning

confidence: 99%

Novel translocation responses of cytosolic phospholipase A2α fluorescent proteins

Wooten

Daniel

Leslie

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Cytosolic phospholipase A2 (cPLA2)alpha responds to the rise in cytosolic Ca2+ ([Ca2+]i) attending cell stimulation by moving to intracellular membranes, releasing arachidonic acid (AA) from these membranes, and thereby initiating the synthesis of various lipid mediators. Under some conditions, however, cPLA2alpha translocation occurs without any corresponding changes in [Ca2+]i. The signal for such responses has not been identified. Using confocal microscopy to track fluorescent proteins fused to cPLA2alpha or cPLA2alpha's C2 domain, we find that AA mimics Ca2+ ionophores in stimulating cPLA(2)alpha translocations to the perinuclear ER and to a novel site, the lipid body. Unlike the ionophores, AA acted independently of [Ca2+](i) rises and did not translocate the proteins to the Golgi. AA's action did not involve its metabolism to eicosanoids or acylation into cellular lipids. Receptor agonists also stimulated translocations targeting lipid bodies. We propose that AA is a signal for Ca2+-independent cPLA2alpha translocation and that lipid bodies are common targets of cPLA2alpha and contributors to stimulus-induced lipid mediator synthesis.

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“…Moreover, baicalein induced apoptosis in renal cell carcinomas in time‐ and concentration‐dependent manner (33). For these reasons, we assume that 12‐LOX pathways play an important role in cancer cell survival (34), and its inhibition might be an effective co‐therapy to hypericin‐mediated PDT.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Hypericin Photodynamic Therapy by Pretreatment with 12 Various Inhibitors of Arachidonic Acid Metabolism in Colon Adenocarcinoma HT‐29 Cells

Kleban

Mikes

Szilárdiová

et al. 2007

Photochem & Photobiology

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One proposal to increase the efficiency of photodynamic therapy (PDT) is to accompany photosensitization with other treatment modalities, including modulation of arachidonic acid (AA) metabolism. The aim of this study was to evaluate the effectiveness of a combined modality approach employing 48 and 24 h pretreatment with various inhibitors of lipoxygenase (LOX; nordihydroguaiaretic acid, esculetin, AA-861, MK-886 and baicalein), cyclooxygenase (COX; diclofenac, flurbiprofen, ibuprofen, indomethacin, SC-560 and rofecoxib) and cytochrome P450-monooxygenase (proadifen) pathways, followed by hypericin-mediated PDT. Cytokinetic parameters like MTT assay, adherent and floating cell numbers, viability and cell cycle distribution analysis were examined 24 h after hypericin activation. Pretreatment of human colon cancer cells HT-29 prior to PDT with 5-LOX inhibitor MK-886 as well as 5, 12-LOX and 12-LOX inhibitors (esculetin and baicalein, respectively) resulted in significant and dose-dependent effects on all parameters tested. Pretreatment with diclofenac, flurbiprofen, ibuprofen and indomethacin, the nonspecific COX inhibitors, promoted hypericin-mediated PDT, but these effects were probably COX-independent. In contrast, application of SC-560 and rofecoxib, specific inhibitors of COX-1 and COX-2, respectively, attenuated PDT. Inhibition of P450 monooxygenase with proadifen implied also the significance of this metabolic pathway in cell survival and cell resistance to hypericin photocytotoxicity. In conclusion, our results testify that application of diverse inhibitors of AA metabolism may have different consequences on cellular response to hypericin-mediated PDT and that some of them could be considered for potentiation of PDT.

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Lipoxygenase Pathway of Arachidonic Acid Metabolism in Growth Control of Tumor Cells of Different Type

Cited by 12 publications

References 27 publications

Inhibition of 12‐LOX and COX‐2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K‐Akt signalling pathways

Inhibition of 12‐LOX and COX‐2 reduces the proliferation of human epidermoid carcinoma cells (A431) by modulating the ERK and PI3K‐Akt signalling pathways

Novel translocation responses of cytosolic phospholipase A2α fluorescent proteins

Modulation of Hypericin Photodynamic Therapy by Pretreatment with 12 Various Inhibitors of Arachidonic Acid Metabolism in Colon Adenocarcinoma HT‐29 Cells

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