Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model
Lung cancer is the most prevalent cancer worldwide. Despite advances in surgery and immune-chemotherapy, the therapeutic outcome remains poor. In recent years, the anticancer properties of natural compounds, along with their low toxic side effects, have attracted the interest of researchers. Resvera...
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MDPI AG
2022-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/1784 |
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| author | Monica Savio Alessandra Ferraresi Chiara Corpina Sara Vandenberghe Chiara Scarlata Virginie Sottile Luca Morini Beatrice Garavaglia Ciro Isidoro Lucia Anna Stivala |
| author_facet | Monica Savio Alessandra Ferraresi Chiara Corpina Sara Vandenberghe Chiara Scarlata Virginie Sottile Luca Morini Beatrice Garavaglia Ciro Isidoro Lucia Anna Stivala |
| author_sort | Monica Savio |
| collection | DOAJ |
| description | Lung cancer is the most prevalent cancer worldwide. Despite advances in surgery and immune-chemotherapy, the therapeutic outcome remains poor. In recent years, the anticancer properties of natural compounds, along with their low toxic side effects, have attracted the interest of researchers. Resveratrol (RSV) and many of its derivatives received particular attention for their beneficial bioactivity. Here we studied the activity of RSV and of its analogue 4,4′-dihydroxystilbene (DHS) in C57BL/6J mice bearing cancers resulting from Lung Lewis Carcinoma (LLC) cell implantation, considering tumour mass weight, angiogenesis, cell proliferation and death, autophagy, as well as characterization of their immune microenvironment, including infiltrating cancer-associated fibroblasts (CAFs). C57BL/6J mice started treatment with RSV or DHS, solubilised in drinking water, one week before LLC implantation, and continued for 21 days, at the end of which they were sacrificed, and the tumour masses collected. Histology was performed according to standard procedures; angiogenesis, cell proliferation and death, autophagy, infiltrating-immune cells, macrophages and fibroblasts were assessed by immunodetection assays. Both stilbenic compounds were able to contrast the tumour growth by increasing apoptosis and autophagy in LLC tumour masses. Additionally, they contrasted the tumour-permissive microenvironment by limiting the infiltration of tumour-associated immune-cells and, more importantly, by counteracting CAF maturation. Therefore, both stilbenes could be employed to synergise with conventional oncotherapies to limit the contribution of stromal cells in tumour growth. |
| first_indexed | 2024-03-09T10:00:31Z |
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| id | doaj.art-7fdda2524712424d9e2accb6733288b0 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:00:31Z |
| publishDate | 2022-07-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7fdda2524712424d9e2accb6733288b02023-12-01T23:26:51ZengMDPI AGBiomedicines2227-90592022-07-01108178410.3390/biomedicines10081784Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine ModelMonica Savio0Alessandra Ferraresi1Chiara Corpina2Sara Vandenberghe3Chiara Scarlata4Virginie Sottile5Luca Morini6Beatrice Garavaglia7Ciro Isidoro8Lucia Anna Stivala9Immunology and General Pathology Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyLaboratory of Molecular Pathology, Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, ItalyImmunology and General Pathology Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyImmunology and General Pathology Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyImmunology and General Pathology Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyImmunology and General Pathology Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyUnit of Legal Medicine, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, ItalyLaboratory of Molecular Pathology, Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, ItalyLaboratory of Molecular Pathology, Department of Health Sciences, University of Piemonte Orientale “A. Avogadro”, 28100 Novara, ItalyImmunology and General Pathology Unit, Department of Molecular Medicine, University of Pavia, 27100 Pavia, ItalyLung cancer is the most prevalent cancer worldwide. Despite advances in surgery and immune-chemotherapy, the therapeutic outcome remains poor. In recent years, the anticancer properties of natural compounds, along with their low toxic side effects, have attracted the interest of researchers. Resveratrol (RSV) and many of its derivatives received particular attention for their beneficial bioactivity. Here we studied the activity of RSV and of its analogue 4,4′-dihydroxystilbene (DHS) in C57BL/6J mice bearing cancers resulting from Lung Lewis Carcinoma (LLC) cell implantation, considering tumour mass weight, angiogenesis, cell proliferation and death, autophagy, as well as characterization of their immune microenvironment, including infiltrating cancer-associated fibroblasts (CAFs). C57BL/6J mice started treatment with RSV or DHS, solubilised in drinking water, one week before LLC implantation, and continued for 21 days, at the end of which they were sacrificed, and the tumour masses collected. Histology was performed according to standard procedures; angiogenesis, cell proliferation and death, autophagy, infiltrating-immune cells, macrophages and fibroblasts were assessed by immunodetection assays. Both stilbenic compounds were able to contrast the tumour growth by increasing apoptosis and autophagy in LLC tumour masses. Additionally, they contrasted the tumour-permissive microenvironment by limiting the infiltration of tumour-associated immune-cells and, more importantly, by counteracting CAF maturation. Therefore, both stilbenes could be employed to synergise with conventional oncotherapies to limit the contribution of stromal cells in tumour growth.https://www.mdpi.com/2227-9059/10/8/1784nutraceuticalsstilbenestumour microenvironmentimmune cellscancer-associated fibroblastsautophagy |
| spellingShingle | Monica Savio Alessandra Ferraresi Chiara Corpina Sara Vandenberghe Chiara Scarlata Virginie Sottile Luca Morini Beatrice Garavaglia Ciro Isidoro Lucia Anna Stivala Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model Biomedicines nutraceuticals stilbenes tumour microenvironment immune cells cancer-associated fibroblasts autophagy |
| title | Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model |
| title_full | Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model |
| title_fullStr | Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model |
| title_full_unstemmed | Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model |
| title_short | Resveratrol and Its Analogue 4,4′-Dihydroxy-trans-stilbene Inhibit Lewis Lung Carcinoma Growth In Vivo through Apoptosis, Autophagy and Modulation of the Tumour Microenvironment in a Murine Model |
| title_sort | resveratrol and its analogue 4 4 dihydroxy trans stilbene inhibit lewis lung carcinoma growth in vivo through apoptosis autophagy and modulation of the tumour microenvironment in a murine model |
| topic | nutraceuticals stilbenes tumour microenvironment immune cells cancer-associated fibroblasts autophagy |
| url | https://www.mdpi.com/2227-9059/10/8/1784 |
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