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

Xiaoping Wang, Huanping Lin, Yan Gu, Xiaoping Wang, Huanping Lin, Yan Gu

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.

Figures

Figure 1
Figure 1
Products of dihomo-γ-linolenic acid. In mammal tissues and cells, DGLA is converted to AA by an alternating sequence of Δ5 desaturation. DGLA can be converted to PG1 via the cyclooxygenase pathway and/or converted to 15-HETrE via the 15-lipoxygenase pathway. During the process of conversion mediated by different oxygenases, free radicals and lipid perioxidation and various metabolites were generated.
Figure 2
Figure 2
Metabolism of dihomo-γ-linolenic acid. In mammal tissues and cells, LA is converted to AA by an alternating sequence of Δ6 desaturation, chain elongation and Δ5 desaturation. Dietary GLA bypasses the rate-limited Δ6 desaturation step and is quickly elongated to DGLA by elongase, with only a very limited amount being desaturated to AA by Δ5 desaturase. DGLA can be converted to PGE1 via the cyclooxygenase pathway and/or converted to 15-HETrE via the 15-lipoxygenase pathway.
Figure 3
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.

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