Multiple roles of dihomo-γ-linolenic acid against proliferation diseases - PubMed (original) (raw)

Review

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

Xiaoping Wang et al. Lipids Health Dis. 2012.

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.

PubMed Disclaimer

Figures

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

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

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.

Cited by

Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies.
Zhu Y, Li M, Rahman ML, Hinkle SN, Wu J, Weir NL, Lin Y, Yang H, Tsai MY, Ferrara A, Zhang C. Zhu Y, et al. PLoS Med. 2019 Sep 13;16(9):e1002910. doi: 10.1371/journal.pmed.1002910. eCollection 2019 Sep. PLoS Med. 2019. PMID: 31518348 Free PMC article.
Zinc Deficiency, Plasma Fatty Acid Profile and Desaturase Activities in Hemodialysis Patients: Is Supplementation Necessary?
Takic M, Zekovic M, Terzic B, Stojsavljevic A, Mijuskovic M, Radjen S, Ristic-Medic D. Takic M, et al. Front Nutr. 2021 Sep 23;8:700450. doi: 10.3389/fnut.2021.700450. eCollection 2021. Front Nutr. 2021. PMID: 34631763 Free PMC article.
Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women's Health Initiative Memory Study.
Harris WS, Luo J, Pottala JV, Margolis KL, Espeland MA, Robinson JG. Harris WS, et al. PLoS One. 2016 Feb 16;11(2):e0147894. doi: 10.1371/journal.pone.0147894. eCollection 2016. PLoS One. 2016. PMID: 26881936 Free PMC article.
Palmitic acid (16:0) competes with omega-6 linoleic and omega-3 ɑ-linolenic acids for FADS2 mediated Δ6-desaturation.
Park HG, Kothapalli KSD, Park WJ, DeAllie C, Liu L, Liang A, Lawrence P, Brenna JT. Park HG, et al. Biochim Biophys Acta. 2016 Feb;1861(2):91-97. doi: 10.1016/j.bbalip.2015.11.007. Epub 2015 Nov 17. Biochim Biophys Acta. 2016. PMID: 26597785 Free PMC article.
Association between red blood cell fatty acids composition and risk of esophageal cancer: a hospital-based case-control study.
Yin H, Wang Y, Chen Y, Shehzad Q, Xiao F. Yin H, et al. Lipids Health Dis. 2025 Mar 20;24(1):101. doi: 10.1186/s12944-025-02531-8. Lipids Health Dis. 2025. PMID: 40114210 Free PMC article.

References

1. Zhang B, Wang P, Zhou Q, Chen C, Zhuo S, Ye Y, He Q, Chen Y, Su Y. The relationships between erythrocyte membrane n-6 to n-3 polyunsaturated fatty acids ratio and blood lipids and C-reactive protein in Chinese adults: an observational study. Biomed Environ Sci. 2011;24:234–242. - PubMed
1. Gomolka B, Siegert E, Blossey K, Schunck WH, Rothe M, Weylandt KH. Analysis of omega-3 and omega-6 fatty acid-derived lipid metabolite formation in human and mouse blood samples. Prostaglandins Other Lipid Mediat. 2011;94:81–87. doi: 10.1016/j.prostaglandins.2010.12.006. - DOI - PubMed
1. Das UN. Essential Fatty acids - a review. Curr Pharm Biotechnol. 2006;7:467–482. doi: 10.2174/138920106779116856. - DOI - PubMed
1. Das UN. Essential fatty acids: biochemistry, physiology and pathology. Biotechnol J. 2006;1:420–439. doi: 10.1002/biot.200600012. - DOI - PubMed
1. Zietemann V, Kröger J, Enzenbach C, Jansen E, Fritsche A, Weikert C, Boeing H, Schulze MB. Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition-Potsdam study. Br J Nutr. 2010;104:1748–1759. doi: 10.1017/S0007114510002916. - DOI - PubMed

Multiple roles of dihomo-γ-linolenic acid against proliferation diseases - PubMed (original) (raw)