DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA

Rahman, Matlubur; Veigas, Jyothi M.; Williams, Paul J.; Fernandes, Gabriel

doi:10.1007/s10549-013-2703-y

Cited by 70 publications

(62 citation statements)

References 60 publications

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“…Because the fat-1 mouse produces a mixture of different n-3 PUFAs, the in vivo function of individual n-3 PUFA in suppression of endometrial cancer need to be further defined. Previous study has shown that DHA is a more potent inhibitor of breast cancer than EPA (44). The high ratio of DHA in total n-3 PUFAs of fat-1 mice (Supplementary Table S4 and S5) and our in vitro data that DHA effectively represses endometrial cancer cell growth, proliferation, and migration Figure 6.…”

Section: Discussionmentioning

confidence: 70%

Inhibition of Endometrial Cancer by n-3 Polyunsaturated Fatty Acids in Preclinical Models

Zheng

Tang

Liu

et al. 2014

Cancer Prevention Research

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Although preclinical and epidemiologic studies have shown the importance of n-3 polyunsaturated fatty acids (PUFA) in the prevention of hormone-responsive cancers such as breast cancer, evidence of the association between n-3 PUFAs and endometrial cancer risk is limited and no previous study has examined the effect of n-3 PUFAs on endometrial cancer in cellular and animal models. In this study, we demonstrated that docosahexenoic acid (DHA) dose-and time-dependently inhibited endometrial cancer cell proliferation, colony formation, and migration and promoted apoptosis. Dietary n-3 PUFAs efficiently prevented endometrial cancer cell growth in xenograft models. Moreover, ectopic expression of fat-1, a desaturase, catalyzed the conversion of n-6 to n-3 PUFAs and produced n-3 PUFAs endogenously, also suppressed endometrial tumor cell growth and migration, and potentiated apoptosis in endometrial cancer cell lines. Interestingly, implanted endometrial cancer cells were unable to grow in fat-1 transgenic SCID mice. Further study revealed that mTOR signaling, which plays an essential role in cell proliferation and endometrial tumorigenesis, is a target of n-3 PUFAs. Exogenous or endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and mTORC2 in vitro and in vivo. Moreover, both dietary n-3 PUFAs and transgenic expression of fat-1 in mice effectively repressed mTORC1/2 signaling and endometrial growth elicited by unopposed estrogen. Taken together, our findings provide comprehensive preclinical evidences that n-3 PUFAs efficiently prevent endometrial cancer and establish mTORC1/2 as a target of n-3 PUFAs. Cancer Prev Res; 7(8); 824-34. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 70%

Inhibition of Endometrial Cancer by n-3 Polyunsaturated Fatty Acids in Preclinical Models

Zheng

Tang

Liu

et al. 2014

Cancer Prevention Research

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“…It was also reported that LNCaP cell growth was inhibited by EPA and DHA (8). The effect of EPA and DHA on the proliferation and invasion of the breast cancer cell lines MDA-MB-231 and MDA-231 Luc and the effect of EPA and DHA on breast cancer metastasis to bone following intracardiac injection of MDA-MB-231 and MDA-231-Luc cells was also evaluated in other studies (9,10). In brief, MDA-MB-231 cells were injected into mice that were fed experimental diets containing EPA or DHA.…”

Section: Discussionmentioning

confidence: 98%

“…In brief, MDA-MB-231 cells were injected into mice that were fed experimental diets containing EPA or DHA. It was concluded that DHA inhibited the proliferation of cancer cells in bone metastasis compared with EPA (9). It was also demonstrated that there is an association between PC3 cell invasion and voltage-gated sodium channels; the data suggested that EPA inhibited the sodium current and downregulated sodium channel function (10).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of PC3 human prostate cancer cell proliferation, invasion and migration by eicosapentaenoic acid and docosahexaenoic acid

et al. 2017

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Abstract. The n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil, exert a number of beneficial effects, and they are used in the treatment of hyperlipidemia. In recent years, EPA and DHA have been found to affect cancer cell proliferation. In the present study, PC3 cells, which are androgen-independent prostate cancer cells that resemble castration-resistant prostate cancer cells, were used to investigate a possible novel treatment for castration-resistant prostate cancer. The PC3 cells were cultured and incubated with various concentrations of EPA or DHA. Cancer proliferation was confirmed by trypan blue microscopy. Invasion and migration assays were used in the upper chamber in PC3 cells, and serum-free medium and various concentrations of EPA or DHA were placed in the lower chamber in serum-containing medium. EPA and DHA decreased PC3 cell proliferation, invasion and migration. The effect of EPA on PC3 cells was dose-dependent and significant differences were observed at concentrations of 100 and 200 µg/ml. The effect of DHA on PC3 cells was similar to that of EPA. In the migration assay, EPA exerted almost no effects at 25 µg/ml, but migration was reduced at 50 µg/ml. Similar to EPA, DHA exerted almost no effects at 25 µg/ml, but further reduction was observed at the 50 µg/ml concentration. In the invasion assay, EPA at 25 µg/ml was not significantly different from the control, but suppressed invasion at 50 µg/ml. DHA decreased invasion compared with the control at 25 µg/ml, whereas invasion was significantly reduced at a DHA concentration of 50 µg/ml. In conclusion, it was demonstrated that EPA and DHA were effective in decreasing the proliferation, invasion and migration of prostate PC3 cancer cells. However, the detailed underlying mechanisms have not yet been fully elucidated. IntroductionEicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids that have several beneficial effects, including decreasing the plasma triglyceride concentration, lipoprotein metabolism (1,2), inhibiting platelet aggregation by collagen (3), and improving the reduced elasticity of the arterial walls through the endothelium-dependent relaxation response in rabbits (4). For these reasons, DHA and EPA are clinically used in Japan. In recent years, n-3 fatty acids have been shown to decrease the proliferation of cancer cells in colon, breast and liver cancer, as well as neuroblastoma. In addition, n-3 fatty acids may be used in cancer cachexia; the combination of chemotherapy and n-3 fatty acids was helpful in the curative as well as the palliative clinical setting (5), but a systematic review did not evaluate the balance of their cost-effectiveness against their utility (6). A number of studies have investigated cancer cell growth; however, only a limited number of studies have examined invasion and metastasis in prostate cancer, which exhibits an increasing prevalence. In the present study, the PC3 prostate cancer cell line was used, which is an androgen-independen...

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“…These studies focused mainly on increasing the dietary intake of PUFAs, in in vivo and clinical studies, or by the use of DHA in its free form in vitro. 3,5,31,33,34 DHA significantly decreased the expression of cytokine-induced leukocyte adhesionmolecule expression in human endothelial cells, while EPA, another member of PUFAs, did not. 33 In a genomic study, Bouwens et al demonstrated that a high oral dose of DHA and EPA decreased the expression of genes involved in inflammatory pathways, such as eicosanoid synthesis, …”

Section: Cell-uptake/interaction Studies Of Liposomesmentioning

confidence: 96%

Docosahexaenoic acid liposomes for targeting chronic inflammatory diseases and cancer: an in vitro assessment

Alaarg¹,

Jordan²,

Verhoef³

et al. 2016

IJN

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Inflammation, oxidative stress, and uncontrolled cell proliferation are common key features of chronic inflammatory diseases, such as atherosclerosis and cancer. ω3 polyunsaturated fatty acids (PUFAs; also known as omega3 fatty acids or fish oil) have beneficial effects against inflammation upon dietary consumption. However, these effects cannot be fully exploited unless diets are enriched with high concentrations of fish oil supplements over long periods of time. Here, a nanomedicine-based approach is presented for delivering effective levels of PUFAs to inflammatory cells. Nanoparticles are internalized by immune cells, and hence can adequately deliver bioactive lipids into these target cells. The ω3 FA docosahexaenoic acid was formulated into liposomes (ω-liposomes), and evaluated for anti-inflammatory effects in different types of immune cells. ω-Liposomes strongly inhibited the release of reactive oxygen species and reactive nitrogen species from human neutrophils and murine macrophages, and also inhibited the production of the proinflammatory cytokines TNFα and MCP1. Moreover, ω-liposomes inhibited tumor-cell proliferation when evaluated in FaDu head and neck squamous carcinoma and 4T1 breast cancer cells in in vitro cultures. We propose that ω-liposomes are a promising nanonutraceutical formulation for intravenous delivery of fish oil FAs, which may be beneficial in the treatment of inflammatory disorders and cancer.

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DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA

Cited by 70 publications

References 60 publications

Inhibition of Endometrial Cancer by n-3 Polyunsaturated Fatty Acids in Preclinical Models

Inhibition of Endometrial Cancer by n-3 Polyunsaturated Fatty Acids in Preclinical Models

Inhibition of PC3 human prostate cancer cell proliferation, invasion and migration by eicosapentaenoic acid and docosahexaenoic acid

Docosahexaenoic acid liposomes for targeting chronic inflammatory diseases and cancer: an in vitro assessment

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