Docosahexaenoic acid and disulfiram act in concert to kill cancer cells: a mutual enhancement of their anticancer actions

Jiao, Yang; Hannafon, Bethany N.; Zhang, Roy R.; Fung, Kar Ming; Ding, Wei

doi:10.18632/oncotarget.14702

Cited by 26 publications

(48 citation statements)

References 59 publications

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“…As shown in Fig. 6a , compared to corn oil diet the fish oil diet suppressed tumor growth in the xenograft model system, consistent with our recent reports [ 23 , 32 ]. The addition of Sorafenib significantly enhanced the suppression of tumor growth in the fish oil diet fed mice (Fig.…”

Section: Resultssupporting

confidence: 91%

“…To test whether Sorafenib enhances DHAs’ anticancer activity in vivo, we implanted MDA-MB-231 cells into nude mice and examined the effects of Sorafenib on tumor growth in the mice fed either a 7.5% fish oil (high n-3 fatty acids/DHA) or 7.5% corn oil (high n-6 fatty acids), see [ 23 , 32 ]). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously reported that DHA acts in concert with clioquinol [ 30 ] and disulfiram [ 32 ] to more effectively kill cancer cells, suggesting that different mechanisms are involved in the synergistic action of DHA and these anticancer compounds. To further test this assumption, we screened the Oncology Drug Set IV using MDA-MB-231 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Athymic nude mice (Foxn1nu) were purchased from Envigo (United Kingdom) and were used for in vivo evaluation of Sorafenib in accordance with the Institute Animal Care and Use Committee procedures and guidelines. The mice were fed either 7.5% (wt/wt) corn oil diet or 7.5% (wt/wt) fish oil diet (enriched in DHA and eicosapentaenoic acid (EPA) as we recently described [ 32 ]) and reported by others [ 6 , 34 – 38 ]. A total of 3 × 10 6 MDA-MB-231 cells were suspended in 100 μL PBS containing 20% Matrigel, and injected s.c. into the flanks of 5-week old female mice.…”

Section: Methodsmentioning

confidence: 99%

“…Animal body weight and tumor volume were measured three times per week [ 31 ]. The tumor volume was calculated using the following formula: v = l × w 2 × 0.5, as we reported [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

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Sorafenib and docosahexaenoic acid act in synergy to suppress cancer cell viability: a role of heme oxygenase 1

et al. 2018

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BackgroundDocosahexaenoic acid (DHA) is a long chain n-3 polyunsaturated fatty acid that has anticancer activity. Heme oxygenase 1 (HO-1) is a potential therapeutic target due to its cytoprotective activity in cancer cells. We recently reported that DHA induces HO-1 gene transcription in human cancer cells by augmenting the degradation of Bach1 protein, which functions as a negative regulator of HO-1. Since the degradation of Bach1 protein relies on protein phosphorylation, we hypothesized that DHA-induced HO-1 gene transcription could be attenuated by kinase inhibitors, resulting in an enhanced cytotoxicity. Sorafenib, a tyrosine kinase inhibitor, was first applied to test our hypothesis.MethodsHuman cancer cell lines and a xenograft nude mouse model were applied to test our hypothesis. Gene expression was analyzed by western blot analysis and reporter gene assay. Cell viability was analyzed using a colorimetric assay. Isobologram was applied to analyze drug action.ResultsPretreatment of cancer cells with Sorafenib significantly attenuated DHA-induced degradation of Bach1 protein. Consequently, DHA-induced HO-1 gene transcription was reversed by Sorafenib as evidenced by western blot and reporter gene analysis. Sorafenib acted synergistically with DHA to suppress cancer cell viability in various human cancer cell lines and suppressed tumor xenograft growth in mice fed a fish oil enriched diet (high n-3/DHA), as compared to mice fed a corn oil (high n-6) diet. Screening of the NCI-Oncology Drug Set IV identified a group of anticancer compounds, including Sorafenib, which enhanced DHA’s cytotoxicity, as well as a set of compounds that attenuated DHA’s cytotoxicity.ConclusionsWe demonstrate that sorafenib attenuates DHA-induced HO-1 expression and acts in synergy with DHA to suppress cancer cell viability and tumor growth. Considering the known health benefits of DHA and the clinical effectiveness of Sorafenib, their combination is an attractive therapeutic strategy against cancer.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Animal body weight and tumor volume were measured three times per week [ 31 ]. The tumor volume was calculated using the following formula: v = l × w 2 × 0.5, as we reported [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

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Sorafenib and docosahexaenoic acid act in synergy to suppress cancer cell viability: a role of heme oxygenase 1

et al. 2018

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Pan‐cancer analyses reveal molecular and clinical characteristics of cuproptosis regulators

Tan

Wang

et al. 2022

iMeta

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Imbalance in copper homeostasis can be lethal to the body. A recent study found that excess copper induces cell death in a way that has never been characterized before, which is dependent on mitochondrial stress and referred to as "cuproptosis." The role of cuproptosis in tumors has not yet been elucidated. In this study, we revealed the complex and important roles of cuproptosis regulators and cuproptosis activity in tumors via a comprehensive analysis of multi-omics data from more than 10 000 samples of 33 tumor types. We found that the cyclin-dependent kinase inhibitor 2A is the most frequently altered cuproptosis regulator, and the cuproptosis regulator expression is dysregulated in various tumors. Additionally, we developed a cuproptosis activity score to re ect the overall cuproptosis level. Based on the expression levels of cuproptosis regulators, tumors can be divided into two clusters with different cuproptosis activities and survival outcomes. Importantly, cuproptosis activity was found to be associated with the prognosis of multiple tumors and multiple tumor-related pathways, including fatty acid metabolism and remodeling of the tumor microenvironment. Furthermore, cuproptosis extensively increased the sensitivity to multiple drugs and exhibited potential to predict the outcome of immunotherapy. We also comprehensively identi ed cuproptosis-related microRNAs, long non-coding RNAs, and transcription factors. In summary, this study reveals important molecular and clinical characteristics of cuproptosis regulators and cuproptosis activity in tumors, and suggests the use of cuproptosis as a promising tumor therapeutic approach. This study provides an important reference point for future cuproptosis-related research.

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The Effect of Dietary n-3 Polyunsaturated Fatty Acids on Non-obese and Obesity-Associated Breast Cancer

Van

Holt²,

Robinson³

et al. 2023

Interdisciplinary Cancer Research

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Docosahexaenoic acid and disulfiram act in concert to kill cancer cells: a mutual enhancement of their anticancer actions

Cited by 26 publications

References 59 publications

Sorafenib and docosahexaenoic acid act in synergy to suppress cancer cell viability: a role of heme oxygenase 1

Sorafenib and docosahexaenoic acid act in synergy to suppress cancer cell viability: a role of heme oxygenase 1

Pan‐cancer analyses reveal molecular and clinical characteristics of cuproptosis regulators

The Effect of Dietary n-3 Polyunsaturated Fatty Acids on Non-obese and Obesity-Associated Breast Cancer

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