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Multiple roles of dihomo-γ-linolenic acid against proliferation diseases.

Wang X, Lin H, Gu Y - Lipids Health Dis (2012)

Bottom Line: Subsequently, DGLA can be further converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1 (PGE1).This is noteworthy because these compounds possess both anti-inflammatory and anti-proliferative properties.Although the mechanism of DGLA has not yet been elucidated, it is significant to anticipate the antitumor potential benefits from DGLA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Pathology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China. wxpphd@yahoo.cn

ABSTRACT
Considerable arguments remain regarding the diverse biological activities of polyunsaturated fatty acids (PUFA). One of the most interesting but controversial dietary approaches focused on the diverse function of dihomo-dietary γ-linolenic acid (DGLA) in anti-inflammation and anti-proliferation diseases, especially for cancers. This strategy is based on the ability of DGLA to interfere in cellular lipid metabolism and eicosanoid (cyclooxygenase and lipoxygenase) biosynthesis. Subsequently, DGLA can be further converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1 (PGE1). This is noteworthy because these compounds possess both anti-inflammatory and anti-proliferative properties. PGE1 could also induce growth inhibition and differentiation of cancer cells. Although the mechanism of DGLA has not yet been elucidated, it is significant to anticipate the antitumor potential benefits from DGLA.

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Mechanisms of dihomo-γ-linolenic acid in anti-proliferation of diseases. DGLA-derived PGE1 has been identified as possessing anti-inflammatory properties that differentiate it from AA-derived PGE2. DGLA could be metabolized into the 15-lipoxygenase product, 15-HETrE, which is capable of inhibiting the synthesis of AA-derived 5-lipoxygenase metabolites and further attenuates the pro-inflammatory products from AA. All types of free radicals (superoxide anion, H2O2, hydroxyl radicals) and lipid peroxides play a role in the induction of apoptosis of tumor cells by the metabolism of DGLA. Selective COX-2 inhibitor could stop AA from converting to PGE2 which are able to stimulate cancer cell proliferation. DGLA may be accumulated through blocking the conversion to AA mediated by selective desaturase inhibitor.
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Figure 3: Mechanisms of dihomo-γ-linolenic acid in anti-proliferation of diseases. DGLA-derived PGE1 has been identified as possessing anti-inflammatory properties that differentiate it from AA-derived PGE2. DGLA could be metabolized into the 15-lipoxygenase product, 15-HETrE, which is capable of inhibiting the synthesis of AA-derived 5-lipoxygenase metabolites and further attenuates the pro-inflammatory products from AA. All types of free radicals (superoxide anion, H2O2, hydroxyl radicals) and lipid peroxides play a role in the induction of apoptosis of tumor cells by the metabolism of DGLA. Selective COX-2 inhibitor could stop AA from converting to PGE2 which are able to stimulate cancer cell proliferation. DGLA may be accumulated through blocking the conversion to AA mediated by selective desaturase inhibitor.

Mentions: Detection of the oxidative metabolism of DGLA into lipoxygenase products has shown that some cell types, including neutrophils, macrophage/monocytes and epidermal cells, metabolize DGLA into the 15-lipoxygenase product, 15-HETrE. Researches suggest that 15-lipoxygenase-derived hydroxy fatty acids inhibit the synthesis of AA-derived 5-lipoxygenase metabolites [11,12,28] (Figure 3). The observations are significant because elevated levels of AA-derived 5-lipoxygenase products, e.g., LTC4 and LTB4, are associated with several pathologic inflammatory, hyperproliferative disorders [61,62]. Studies also indicate that 15-HETrE can be incorporated into the membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2), and released as 15-HETrE-containing-diacylglycerol (15-HETrE-DAG) [63,64]. Interestingly, 15-HETrE-DAG is able to inhibit protein kinase C β (PKC β), a mediator of the cell cycle in select cell types [63]. The inhibitions of leukotriene biosynthesis and PKC-dependent signal transduction are probable mechanisms by which DGLA exertsanti-inflammation and anti-proliferative responses. It is generally thought that DGLA-derived eicosanoid (PGE1 and 15-HETrE) biosynthesis is dependent primarily on the abundance of nonesterified DGLA, so increasing the administration of DGLA may be a good strategy to treat some proliferation diseases.


Multiple roles of dihomo-γ-linolenic acid against proliferation diseases.

Wang X, Lin H, Gu Y - Lipids Health Dis (2012)

Mechanisms of dihomo-γ-linolenic acid in anti-proliferation of diseases. DGLA-derived PGE1 has been identified as possessing anti-inflammatory properties that differentiate it from AA-derived PGE2. DGLA could be metabolized into the 15-lipoxygenase product, 15-HETrE, which is capable of inhibiting the synthesis of AA-derived 5-lipoxygenase metabolites and further attenuates the pro-inflammatory products from AA. All types of free radicals (superoxide anion, H2O2, hydroxyl radicals) and lipid peroxides play a role in the induction of apoptosis of tumor cells by the metabolism of DGLA. Selective COX-2 inhibitor could stop AA from converting to PGE2 which are able to stimulate cancer cell proliferation. DGLA may be accumulated through blocking the conversion to AA mediated by selective desaturase inhibitor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3295719&req=5

Figure 3: Mechanisms of dihomo-γ-linolenic acid in anti-proliferation of diseases. DGLA-derived PGE1 has been identified as possessing anti-inflammatory properties that differentiate it from AA-derived PGE2. DGLA could be metabolized into the 15-lipoxygenase product, 15-HETrE, which is capable of inhibiting the synthesis of AA-derived 5-lipoxygenase metabolites and further attenuates the pro-inflammatory products from AA. All types of free radicals (superoxide anion, H2O2, hydroxyl radicals) and lipid peroxides play a role in the induction of apoptosis of tumor cells by the metabolism of DGLA. Selective COX-2 inhibitor could stop AA from converting to PGE2 which are able to stimulate cancer cell proliferation. DGLA may be accumulated through blocking the conversion to AA mediated by selective desaturase inhibitor.
Mentions: Detection of the oxidative metabolism of DGLA into lipoxygenase products has shown that some cell types, including neutrophils, macrophage/monocytes and epidermal cells, metabolize DGLA into the 15-lipoxygenase product, 15-HETrE. Researches suggest that 15-lipoxygenase-derived hydroxy fatty acids inhibit the synthesis of AA-derived 5-lipoxygenase metabolites [11,12,28] (Figure 3). The observations are significant because elevated levels of AA-derived 5-lipoxygenase products, e.g., LTC4 and LTB4, are associated with several pathologic inflammatory, hyperproliferative disorders [61,62]. Studies also indicate that 15-HETrE can be incorporated into the membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2), and released as 15-HETrE-containing-diacylglycerol (15-HETrE-DAG) [63,64]. Interestingly, 15-HETrE-DAG is able to inhibit protein kinase C β (PKC β), a mediator of the cell cycle in select cell types [63]. The inhibitions of leukotriene biosynthesis and PKC-dependent signal transduction are probable mechanisms by which DGLA exertsanti-inflammation and anti-proliferative responses. It is generally thought that DGLA-derived eicosanoid (PGE1 and 15-HETrE) biosynthesis is dependent primarily on the abundance of nonesterified DGLA, so increasing the administration of DGLA may be a good strategy to treat some proliferation diseases.

Bottom Line: Subsequently, DGLA can be further converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1 (PGE1).This is noteworthy because these compounds possess both anti-inflammatory and anti-proliferative properties.Although the mechanism of DGLA has not yet been elucidated, it is significant to anticipate the antitumor potential benefits from DGLA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Pathology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China. wxpphd@yahoo.cn

ABSTRACT
Considerable arguments remain regarding the diverse biological activities of polyunsaturated fatty acids (PUFA). One of the most interesting but controversial dietary approaches focused on the diverse function of dihomo-dietary γ-linolenic acid (DGLA) in anti-inflammation and anti-proliferation diseases, especially for cancers. This strategy is based on the ability of DGLA to interfere in cellular lipid metabolism and eicosanoid (cyclooxygenase and lipoxygenase) biosynthesis. Subsequently, DGLA can be further converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1 (PGE1). This is noteworthy because these compounds possess both anti-inflammatory and anti-proliferative properties. PGE1 could also induce growth inhibition and differentiation of cancer cells. Although the mechanism of DGLA has not yet been elucidated, it is significant to anticipate the antitumor potential benefits from DGLA.

Show MeSH
Related in: MedlinePlus