Biotransformation of the SDG in defatted flaxseed into END co-cultured by three single bacterial colonies

Zhu, Hong-Yun; Li, Miaoxin; Yang, Donghui; Tao, Yilun; Zhang, Ying; Liu, Shulin

doi:10.1016/j.procbio.2013.10.003

Cited by 8 publications

(7 citation statements)

References 26 publications

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“…Lignans with anticancer activities, abundant in food materials such as those in flaxseeds [11, 12], have great potential for cancer prevention and treatment as they may reduce the incidence of various cancer types [14, 31, 36, 37]. However, their specific effects on ovarian cancer have not been adequately documented.…”

Section: Discussionmentioning

confidence: 99%

Enterolactone has stronger effects than enterodiol on ovarian cancer

Liu

Wang

et al. 2017

J Ovarian Res

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BackgroundOvarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented.MethodsWe used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL.ResultsThe in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development.ConclusionEND and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.

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Section: Discussionmentioning

confidence: 99%

Enterolactone has stronger effects than enterodiol on ovarian cancer

Liu

Wang

et al. 2017

J Ovarian Res

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“…6846) was isolated from human feces in our previous study (Zhu et al 2014) and grown in anaerobic broth medium (Land Bridge Technology, Beijing, China) under anoxic conditions at 37°C. E. coli Trans1-T1 (TransGen Biotech, Beijing, China) was the host for preparing all recombinant vectors.…”

Section: Methodsmentioning

confidence: 99%

“…The reference standards of secoisolariciresinol (SECO), 3-demethyl-secoisolariciresinol (DMSE), and 4, 4′-dihydroxyenterodiol (DHEND) were isolated, purified, and identified from the fermentation liquid of B. uniformis ZL-I and E. limosum ZL-II using defatted flaxseed as the substrate in our previous study (Wang et al 2000;Xie et al 2003;Zhu et al 2014).…”

Section: Chemicals and Materialsmentioning

confidence: 99%

Cloning, expression, and characterization of a four-component O-demethylase from human intestinal bacterium Eubacterium limosum ZL-II

Chen

Deng

Zhang

et al. 2016

Appl Microbiol Biotechnol

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Eubacterium limosum ZL-II was described to convert secoisolariciresinol (SECO) to its demethylating product 4,4'-dihydroxyenterodiol (DHEND) under anoxic conditions. However, the reaction cascade remains unclear. Here, the O-demethylase being responsible for the conversion was identified and characterized. Nine genes encoding two methyltransferase-Is (MT-I), two corrinoid proteins (CP), two methyltransferase-IIs (MT-II), and three activating enzymes (AE) were screened, cloned, and expressed in Escherichia coli. Four of the nine predicted enzymes, including ELI_2003 (MT-I), ELI_2004 (CP), ELI_2005 (MT-II), and ELI_0370 (AE), were confirmed to constitute the O-demethylase in E. limosum ZL-II. The complete O-demethylase (combining the four components) reaction system was reconstructed in vitro. As expected, the demethylating products 3-demethyl-SECO and DHEND were both produced. During the reaction process, ELI_2003 (MT-I) initially catalyzed the transfer of methyl group from SECO to the corrinoid of ELI_2004 ([Co]-CP), yielding demethylating products and [CH-Co]-CP; then ELI_2005 (MT-II) mediated the transfer of methyl group from [CH-Co]-CP to tetrahydrofolate, forming methyltetrahydrofolate and [Co]-CP. Due to the low redox potential of [Co]/[Co], [Co]-CP was oxidized to [Co]-CP immediately in vitro, and ELI_0370 (AE) was responsible for catalyzing the reduction of [Co]-CP to its active form [Co]-CP. The active-site residues in ELI_2003, ELI_2005, and ELI_0370 were subsequently determined using molecular modeling combined with site-directed mutagenesis. To our knowledge, this is the first study on the identification and characterization of a four-component O-demethylase from E. limosum ZL-II, which will facilitate the development of method to artificial synthesis of related bioactive chemicals.

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“…Plant lignans [39], different from lignins (racemic polymers that are components of the plant cell wall [39,40]), are non-nutrient, noncaloric, bioactive phenolic plant compounds [39]. Diverse lignanoid constituents from plant-based food resources [41], like secoisolariciresinol diglucoside (SDG) [42], lariciresinol [41], isolariciresinol [43], 7-hydroxymatairesinol [44], matairesinol (MAT) [45], pinoresinol, arctigenin, syringaresinol [46], and asarinin [47], can be precursors of enterolignans—the mammalian-derived lignans—following oral consumption of plant lignans [39]. The primary intent of this review is to consolidate the evidence of lignan pharmacokinetics and modulation of cellular processes and cell signaling pathways within the cancer phenotype so as to provide opportunity to direct future investigations into the role and benefit of the dietary polyphenols, specifically flaxseed lignans, in the prevention and treatment of cancer (i.e., complementary and integrative medicine [48]).…”

Section: Introductionmentioning

confidence: 99%

Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets

2019

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Cancer causes considerable morbidity and mortality across the world. Socioeconomic, environmental, and lifestyle factors contribute to the increasing cancer prevalence, bespeaking a need for effective prevention and treatment strategies. Phytochemicals like plant polyphenols are generally considered to have anticancer, anti-inflammatory, antiviral, antimicrobial, and immunomodulatory effects, which explain their promotion for human health. The past several decades have contributed to a growing evidence base in the literature that demonstrate ability of polyphenols to modulate multiple targets of carcinogenesis linking models of cancer characteristics (i.e., hallmarks and nutraceutical-based targeting of cancer) via direct or indirect interaction or modulation of cellular and molecular targets. This evidence is particularly relevant for the lignans, an ubiquitous, important class of dietary polyphenols present in high levels in food sources such as flaxseed. Literature evidence on lignans suggests potential benefit in cancer prevention and treatment. This review summarizes the relevant chemical and pharmacokinetic properties of dietary polyphenols and specifically focuses on the biological targets of flaxseed lignans. The consolidation of the considerable body of data on the diverse targets of the lignans will aid continued research into their potential for use in combination with other cancer chemotherapies, utilizing flaxseed lignan-enriched natural products.

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Biotransformation of the SDG in defatted flaxseed into END co-cultured by three single bacterial colonies

Cited by 8 publications

References 26 publications

Enterolactone has stronger effects than enterodiol on ovarian cancer

Enterolactone has stronger effects than enterodiol on ovarian cancer

Cloning, expression, and characterization of a four-component O-demethylase from human intestinal bacterium Eubacterium limosum ZL-II

Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets

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