ArticleThe Journal of nutritional biochemistry2014
Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation.
Article in The Journal of nutritional biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 22 citations in OpenAlex.
- Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.Biomarker research · 2024Review
- Lipopolysaccharide Tolerance in Human Primary Monocytes and Polarized Macrophages.International journal of molecular sciences · 2023Article
- Pronounced Enhancement in Radiosensitization of Esophagus Cancer Cultivated in Docosahexaenoic Acid via theFrontiers in medicine · 2022Article
- Changes in the expression levels of elastic fibres in yak lungs at different growth stages.BMC developmental biology · 2021Article
- Natural Product Heme Oxygenase Inducers as Treatment for Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2020Review
- Sorafenib and docosahexaenoic acid act in synergy to suppress cancer cell viability: a role of heme oxygenase 1.BMC cancer · 2018Article
- Docosahexaenoic Acid (DHA) Provides Neuroprotection in Traumatic Brain Injury Models via Activating Nrf2-ARE Signaling.Inflammation · 2018Article
- Docosahexaenoic acid and disulfiram act in concert to kill cancer cells: a mutual enhancement of their anticancer actions.Oncotarget · 2017Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The effect of docosahexaenoic acid (DHA) on heme oxygenase-1 (HO-1) expression in cancer cells has never been characterized. This study examines DHA-induced HO-1 expression in human cancer cell model systems. DHA enhanced HO-1 gene expression in a time- and concentration-dependent manner, with maximal induction at 21 h of treatment. This induction of HO-1 expression was confirmed in vivo using a xenograft nude mouse model fed a fish-oil-enriched diet. The increase in HO-1 gene transcription induced by DHA was significantly attenuated by the antioxidant N-acetyl cysteine, suggesting the involvement of oxidative stress. This was supported by direct measurement of lipid peroxide levels after DHA treatment. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediate the DHA-induced increase in HO-1 gene transcription. Knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression compromised the DHA-induced increase in HO-1 gene transcription, indicating the importance of the Nrf2 pathway in this event. However, the nuclear protein levels of Nrf2 remained unchanged upon DHA treatment. Further studies demonstrated that DHA reduces nuclear Bach1 protein expression by promoting its degradation and attenuates Bach1 binding to the AREs in the HO-1 gene promoter. In contrast, DHA enhanced Nrf2 binding to the AREs without affecting nuclear Nrf2 expression levels, indicating a new cellular mechanism that mediates DHA's induction of HO-1 gene transcription. To our knowledge, this is the first characterization of DHA-induced HO-1 expression in human malignant cells.
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