Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation
Previous studies demonstrated that enzymatic hydrolysis enhances wheat bran (WB) biological properties. This study evaluated the immunostimulatory effect of a WB hydrolysate (HYD) and a mousse enriched with HYD (MH) before and after in vitro digestion on murine and human macrophages. The antiprolife...
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7436 |
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| author | Irene Tomé-Sánchez Cristina Martínez-Villaluenga Ana Belén Martín-Diana Daniel Rico Iván Jiménez-Pulido Juana Frias Vermont P. Dia |
| author_facet | Irene Tomé-Sánchez Cristina Martínez-Villaluenga Ana Belén Martín-Diana Daniel Rico Iván Jiménez-Pulido Juana Frias Vermont P. Dia |
| author_sort | Irene Tomé-Sánchez |
| collection | DOAJ |
| description | Previous studies demonstrated that enzymatic hydrolysis enhances wheat bran (WB) biological properties. This study evaluated the immunostimulatory effect of a WB hydrolysate (HYD) and a mousse enriched with HYD (MH) before and after in vitro digestion on murine and human macrophages. The antiproliferative activity of the harvested macrophage supernatant on colorectal cancer (CRC) cells was also analyzed. MH showed significantly higher content than control mousse (M) in soluble poly- and oligosaccharides (OLSC), as well as total soluble phenolic compounds (TSPC). Although in vitro gastrointestinal digestion slightly reduced the TSPC bioaccessibility of MH, ferulic acid (FA) levels remained stable. HYD showed the highest antioxidant activity followed by MH, which demonstrated a greater antioxidant activity before and after digestion as compared with M. RAW264.7 and THP-1 cells released the highest amounts of pro-inflammatory cytokines after being treated with 0.5 mg/mL of digested WB samples. Treatment with digested HYD-stimulated RAW264.7 supernatant for 96 h showed the most anticancer effect, and spent medium reduced cancer cell colonies more than direct WB sample treatments. Although a lack of inner mitochondrial membrane potential alteration was found, increased Bax:Bcl-2 ratio and caspase-3 expression suggested activation of the mitochondrial apoptotic pathway when CRC cells were treated with macrophage supernatants. Intracellular reactive oxygen species (ROS) were positively correlated with the cell viability in CRC cells exposed to RAW264.7 supernatants (r = 0.78, <i>p</i> < 0.05) but was not correlated in CRC cells treated with THP-1 conditioned media. Supernatant from WB-stimulated THP-1 cells may be able to stimulate ROS production in HT-29 cells, leading to a decrease of viable cells in a time-dependent manner. Therefore, our present study revealed a novel anti-tumour mechanism of HYD through the stimulation of cytokine production in macrophages and the indirect inhibition of cell proliferation, colony formation, and activation of pro-apoptotic proteins expression in CRC cells. |
| first_indexed | 2024-03-11T04:55:54Z |
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| id | doaj.art-39d48a4b32454f0c84b54aa2260ebc82 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:55:54Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-39d48a4b32454f0c84b54aa2260ebc822023-11-17T19:40:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248743610.3390/ijms24087436Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages StimulationIrene Tomé-Sánchez0Cristina Martínez-Villaluenga1Ana Belén Martín-Diana2Daniel Rico3Iván Jiménez-Pulido4Juana Frias5Vermont P. Dia6Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), José Antonio Novais, 6, 28040 Madrid, SpainInstitute of Food Science, Technology and Nutrition (ICTAN-CSIC), José Antonio Novais, 6, 28040 Madrid, SpainAgricultural Technological Institute of Castilla and Leon, Government of Castilla and Leon, Finca Zamadueñas, Castilla and Leon, 47071 Valladolid, SpainAgricultural Technological Institute of Castilla and Leon, Government of Castilla and Leon, Finca Zamadueñas, Castilla and Leon, 47071 Valladolid, SpainAgricultural Technological Institute of Castilla and Leon, Government of Castilla and Leon, Finca Zamadueñas, Castilla and Leon, 47071 Valladolid, SpainInstitute of Food Science, Technology and Nutrition (ICTAN-CSIC), José Antonio Novais, 6, 28040 Madrid, SpainDepartment of Food Science, The University of Tennessee Institute of Agriculture, Knoxville, TN 37996, USAPrevious studies demonstrated that enzymatic hydrolysis enhances wheat bran (WB) biological properties. This study evaluated the immunostimulatory effect of a WB hydrolysate (HYD) and a mousse enriched with HYD (MH) before and after in vitro digestion on murine and human macrophages. The antiproliferative activity of the harvested macrophage supernatant on colorectal cancer (CRC) cells was also analyzed. MH showed significantly higher content than control mousse (M) in soluble poly- and oligosaccharides (OLSC), as well as total soluble phenolic compounds (TSPC). Although in vitro gastrointestinal digestion slightly reduced the TSPC bioaccessibility of MH, ferulic acid (FA) levels remained stable. HYD showed the highest antioxidant activity followed by MH, which demonstrated a greater antioxidant activity before and after digestion as compared with M. RAW264.7 and THP-1 cells released the highest amounts of pro-inflammatory cytokines after being treated with 0.5 mg/mL of digested WB samples. Treatment with digested HYD-stimulated RAW264.7 supernatant for 96 h showed the most anticancer effect, and spent medium reduced cancer cell colonies more than direct WB sample treatments. Although a lack of inner mitochondrial membrane potential alteration was found, increased Bax:Bcl-2 ratio and caspase-3 expression suggested activation of the mitochondrial apoptotic pathway when CRC cells were treated with macrophage supernatants. Intracellular reactive oxygen species (ROS) were positively correlated with the cell viability in CRC cells exposed to RAW264.7 supernatants (r = 0.78, <i>p</i> < 0.05) but was not correlated in CRC cells treated with THP-1 conditioned media. Supernatant from WB-stimulated THP-1 cells may be able to stimulate ROS production in HT-29 cells, leading to a decrease of viable cells in a time-dependent manner. Therefore, our present study revealed a novel anti-tumour mechanism of HYD through the stimulation of cytokine production in macrophages and the indirect inhibition of cell proliferation, colony formation, and activation of pro-apoptotic proteins expression in CRC cells.https://www.mdpi.com/1422-0067/24/8/7436hydrolyzed wheat brancolorectal cancerimmunomodulationanticancer activityantioxidant activityapoptosis |
| spellingShingle | Irene Tomé-Sánchez Cristina Martínez-Villaluenga Ana Belén Martín-Diana Daniel Rico Iván Jiménez-Pulido Juana Frias Vermont P. Dia Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation International Journal of Molecular Sciences hydrolyzed wheat bran colorectal cancer immunomodulation anticancer activity antioxidant activity apoptosis |
| title | Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation |
| title_full | Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation |
| title_fullStr | Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation |
| title_full_unstemmed | Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation |
| title_short | Antioxidant, Immunostimulatory, and Anticancer Properties of Hydrolyzed Wheat Bran Mediated through Macrophages Stimulation |
| title_sort | antioxidant immunostimulatory and anticancer properties of hydrolyzed wheat bran mediated through macrophages stimulation |
| topic | hydrolyzed wheat bran colorectal cancer immunomodulation anticancer activity antioxidant activity apoptosis |
| url | https://www.mdpi.com/1422-0067/24/8/7436 |
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