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Flavonoids and Cancer Prevention
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Flavonoids and Cancer Prevention

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 53831

Special Issue Editors

Dr. Laura Masuelli

E-Mail Website
Guest Editor
Department of Experimental Medicine, University of Rome “Sapienza”, 00164 Rome, Italy
Interests: cancer; cancer target therapy; nutraceutics; cancer vaccines; extracellular vesicles; biomarkers; ultrastructural pathology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Roberto Bei

E-Mail Website
Guest Editor
Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: cancer immunotherapy; natural compounds and cancer; cancer vaccines; cancer prevention and treatment in preclinical models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Polyphenols constitute one of the most numerous and widely distributed groups of natural products in the plant kingdom. Flavonoids are part of this family and have more than 4000 varieties. Epidemiological studies have shown the association between the consumption of fruits and vegetables and the prevention of human diseases, including cancer. Flavonoids can be employed to inhibit the growth of cancer cells due to their ability to modulate the activity of multiple targets involved in carcinogenesis through simultaneous direct interaction or modulation of gene expression. Unfortunately, so far, flavonoids have a poor bioavailability as well as rapid and extensive metabolism, which prevent reaching physiologically relevant concentrations. Despite this, flavonoids or flavonoid derivatives could be valuable tools for the chemoprevention of cancer.

This Special Issue of Nutrients, entitled “Flavonoids and Cancer prevention”, welcomes the submission of manuscripts that include either original research or reviewing the scientific literature and provide a better understanding of the effects of flavonoids on cancer prevention and treatment, including preclinical and clinical studies.

Assoc. Prof. Dr. Laura Masuelli
Prof. Dr. Roberto Bei
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Flavonoids
  • Cancer
  • Cancer prevention
  • Biological activities
  • Molecular target
  • Cell signaling
  • Dietary flavonoids
  • Bioavailability

Published Papers (7 papers)

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Research

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22 pages, 4291 KiB  
Article
Curcumin Enhances the Antitumoral Effect Induced by the Recombinant Vaccinia Neu Vaccine (rV-neuT) in Mice with Transplanted Salivary Gland Carcinoma Cells
by Chiara Focaccetti, Monica Benvenuto, Sara Ciuffa, Sara Fazi, Manuel Scimeca, Alessandra Nardi, Martino Tony Miele, Andrea Battisti, Elena Bonanno, Andrea Modesti, Laura Masuelli and Roberto Bei
Nutrients 2020, 12(5), 1417; https://doi.org/10.3390/nu12051417 - 14 May 2020
Cited by 12 | Viewed by 2595
Abstract
The survival rate for head and neck cancer patients has not substantially changed in the last two decades. We previously showed that two rV-neuT intratumoral injections induced an efficient antitumor response and rejection of transplanted Neu (rat ErbB2/neu oncogene-encoded protein)-overexpressing salivary [...] Read more.
The survival rate for head and neck cancer patients has not substantially changed in the last two decades. We previously showed that two rV-neuT intratumoral injections induced an efficient antitumor response and rejection of transplanted Neu (rat ErbB2/neu oncogene-encoded protein)-overexpressing salivary gland tumor cells in BALB-neuT mice (BALB/c mice transgenic for the rat ErbB2/neu oncogene). However, reiterated poxviral vaccinations increase neutralizing antibodies to viral proteins in humans that prevent immune response against the recombinant antigen expressed by the virus. Curcumin (CUR) is a polyphenol with antineoplastic and immunomodulatory properties. The aim of this study was to employ CUR administration to boost the anti-Neu immune response and anticancer activity induced by one rV-neuT intratumoral vaccination in BALB-neuT mice. Here, we demonstrated that the combined rV-neuT+CUR treatment was more effective at reducing tumor growth and increasing mouse survival, anti-Neu humoral response, and IFN-γ/IL-2 T-cell release in vitro than the individual treatment. rV-neuT+CUR-treated mice showed an increased infiltration of CD4+/CD8+ T lymphocytes within the tumor as compared to those that received the individual treatment. Overall, CUR enhanced the antitumoral effect and immune response to Neu induced by the rV-neuT vaccine in mice. Thus, the combined treatment might represent a successful strategy to target ErbB2/Neu-overexpressing tumors. Full article
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
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16 pages, 1994 KiB  
Article
An Extract of Olive Mill Wastewater Downregulates Growth, Adhesion and Invasion Pathways in Lung Cancer Cells: Involvement of CXCR4
by Matteo Gallazzi, Marco Festa, Paola Corradino, Clementina Sansone, Adriana Albini and Douglas M. Noonan
Nutrients 2020, 12(4), 903; https://doi.org/10.3390/nu12040903 - 26 Mar 2020
Cited by 15 | Viewed by 2671
Abstract
Several diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects in numerous cancers and could be beneficial in cancer prevention. Olive oil production involves the generation of an aqueous phase defined as olive mill wastewater (OMWW), a polluting effluent rich [...] Read more.
Several diet-derived compounds have been reported to exert antioxidant, anti-proliferative and anti-angiogenic effects in numerous cancers and could be beneficial in cancer prevention. Olive oil production involves the generation of an aqueous phase defined as olive mill wastewater (OMWW), a polluting effluent rich in soluble polyphenols. Here, we assessed the cancer preventive properties exerted by a purified extract of OMWW (A009) for its activity on lung cancer cell lines. Hydroxytyrosol, the most abundant polyphenol present in our A009 extracts, was used as reference molecule in the assays performed. Extracts from OMWW from two different olive oil cultivars were used. We found that the A009 extracts limit lung cancer cell proliferation in a dose and time dependent manner. These effects were associated with the induction of apoptosis. A009 extracts were effective in inhibiting adhesion capabilities on a fibronectin layer accompanied with a reduction in their ability to generate invasive sprouts in a Matrigel layer. The production of chemokine CXCL12 and CXCR4 receptor were reduced by treatment with the extracts. Also, A009 interfered with the production of proangiogenic and pro-inflammatory VEGF, CXCL8, and CCL2 (as detected by FACS analysis) in the lung cell lines. A009 extracts were able to decrease STAT3 phosphorylation in lung cancer cells. Our results show that A009 extracts reduced activities related to tumor cell behavior in lung cancer cell lines, suggesting that they could have a potential cancer preventive role. Full article
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
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18 pages, 3611 KiB  
Article
Gardenia jasminoides Enhances CDDP-Induced Apoptosis of Glioblastoma Cells via AKT/mTOR Pathway While Protecting Death of Astrocytes
by Hyo In Kim, Se Hyang Hong, Jin Mo Ku, Min Jeong Kim, Sung Wan Ju, Seok Won Chang, Chunhoo Cheon and Seong-Gyu Ko
Nutrients 2020, 12(1), 196; https://doi.org/10.3390/nu12010196 - 10 Jan 2020
Cited by 10 | Viewed by 3027
Abstract
Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required. Gardenia jasminoides (GJ) is flavonoid abundant with [...] Read more.
Gliomas are the most observed primary brain tumor, of which glioblastoma multiform (GBM) shows the highest incidence. Radiotherapy with temozolomide is the standard therapeutic method, but because of side effects, search for alternative therapies is required. Gardenia jasminoides (GJ) is flavonoid abundant with beneficial effects on inflammation, metabolic diseases, and cancers. In this study, we investigated the synergistic combination of GJ and cisplatin (CDDP) in U87MG and U373MG GBM cells. GJ and CDDP both showed cytotoxicity in U87MG cells, however GJ did not affect viability of normal astrocytes while CDDP displayed high toxicity. Cytotoxic effect of GJ and CDDP was related in apoptosis when confirmed by Western blot assays on cleaved caspase-3, caspase-9, and PARP. Moreover, GJ and CDDP showed synergistic combination in cell death of GBM cells, which was further confirmed by Western blot assays of apoptosis factors and also flow cytometry of Annexin V. Analysis on autophagy factors showed that GJ/CDDP combination induced autophagy, and through inhibition of autophagy, we could confirm autophagy is crucial to cytotoxicity of GJ/CDDP in GBM cell lines. The autophagy-mediated apoptosis of GJ/CDDP was dependent on the AKT/mTOR pathway. Overall, our results suggest GJ/CDDP combination as an effective yet safe therapeutic approach to GBMs. Full article
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
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18 pages, 1554 KiB  
Article
Estrogenic, Antiestrogenic and Antiproliferative Activities of Euphorbia bicolor (Euphorbiaceae) Latex Extracts and Its Phytochemicals
by Paramita Basu, Elizabeth Meza, Michael Bergel and Camelia Maier
Nutrients 2020, 12(1), 59; https://doi.org/10.3390/nu12010059 - 25 Dec 2019
Cited by 7 | Viewed by 3705
Abstract
Estrogen receptor antagonists are effective in breast cancer treatment. However, the side effects of these treatments have led to a rise in searching for alternative therapies. The present study evaluated the estrogenic, antiestrogenic, and antiproliferative activities of Euphorbia bicolor (Euphorbiaceae), a [...] Read more.
Estrogen receptor antagonists are effective in breast cancer treatment. However, the side effects of these treatments have led to a rise in searching for alternative therapies. The present study evaluated the estrogenic, antiestrogenic, and antiproliferative activities of Euphorbia bicolor (Euphorbiaceae), a plant native to south-central USA. Estrogenic and antiestrogenic activities of latex extract and its phytochemicals were evaluated with a steroid-regulated yeast system expressing the human estrogen receptor α and antiproliferative properties were assessed in the ER-positive MCF-7 and T47-D and triple-negative MDA-MB-231 and MDA-MB-469 breast carcinomas. Genistein and coumestrol identified in the latex extract induced higher estrogenic and antiestrogenic activities compared to diterpenes and flavonoids. The latex extract, resiniferatoxin (RTX) and rutin induced antiproliferative activities in all cell lines in a dose-dependent manner, but not in human normal primary dermal fibroblast cultures. A biphasic effect was observed with MDA-MB-468 breast carcinoma in which the latex extract at low concentrations increased and at high concentrations decreased cell proliferation. Treatments with latex extract in combination with RTX or rutin reduced even more the proliferation of MCF-7 breast carcinoma compared to the individual latex, RTX, and rutin treatments. E. bicolor latex phytochemicals could contribute to developing commercial therapeutic agents for breast cancer treatment. Full article
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
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Review

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24 pages, 2117 KiB  
Review
Flavonoids as Epigenetic Modulators for Prostate Cancer Prevention
by Simona Izzo, Valeria Naponelli and Saverio Bettuzzi
Nutrients 2020, 12(4), 1010; https://doi.org/10.3390/nu12041010 - 06 Apr 2020
Cited by 38 | Viewed by 5998
Abstract
Prostate cancer (PCa) is a multifactorial disease with an unclear etiology. Due to its high prevalence, long latency, and slow progression, PCa is an ideal target for chemoprevention strategies. Many research studies have highlighted the positive effects of natural flavonoids on chronic diseases, [...] Read more.
Prostate cancer (PCa) is a multifactorial disease with an unclear etiology. Due to its high prevalence, long latency, and slow progression, PCa is an ideal target for chemoprevention strategies. Many research studies have highlighted the positive effects of natural flavonoids on chronic diseases, including PCa. Different classes of dietary flavonoids exhibit anti-oxidative, anti-inflammatory, anti-mutagenic, anti-aging, cardioprotective, anti-viral/bacterial and anti-carcinogenic properties. We overviewed the most recent evidence of the antitumoral effects exerted by dietary flavonoids, with a special focus on their epigenetic action in PCa. Epigenetic alterations have been identified as key initiating events in several kinds of cancer. Many dietary flavonoids have been found to reverse DNA aberrations that promote neoplastic transformation, particularly for PCa. The epigenetic targets of the actions of flavonoids include oncogenes and tumor suppressor genes, indirectly controlled through the regulation of epigenetic enzymes such as DNA methyltransferase (DNMT), histone acetyltransferase (HAT), and histone deacetylase (HDAC). In addition, flavonoids were found capable of restoring miRNA and lncRNA expression that is altered during diseases. The optimization of the use of flavonoids as natural epigenetic modulators for chemoprevention and as a possible treatment of PCa and other kinds of cancers could represent a promising and valid strategy to inhibit carcinogenesis and fight cancer. Full article
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
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18 pages, 576 KiB  
Review
Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer
by Priyanga Selvakumar, Aja Badgeley, Paige Murphy, Hina Anwar, Urvashi Sharma, Katharine Lawrence and Ashakumary Lakshmikuttyamma
Nutrients 2020, 12(3), 761; https://doi.org/10.3390/nu12030761 - 13 Mar 2020
Cited by 105 | Viewed by 9559
Abstract
Breast cancer is a common cancer that occurs due to different epigenetic alterations and genetic mutations. Various epidemiological studies have demonstrated an inverse correlation between breast cancer incidence and flavonoid intake. The anti-cancer action of flavonoids, a class of polyphenolic compounds that are [...] Read more.
Breast cancer is a common cancer that occurs due to different epigenetic alterations and genetic mutations. Various epidemiological studies have demonstrated an inverse correlation between breast cancer incidence and flavonoid intake. The anti-cancer action of flavonoids, a class of polyphenolic compounds that are present in plants, as secondary metabolites has been a major topic of research for many years. Our review analysis demonstrates that flavonoids exhibit anti-cancer activity against breast cancer occurring in different ethnic populations. Breast cancer subtype and menopausal status are the key factors in inducing the flavonoid’s anti-cancer action in breast cancer. The dose is another key factor, with research showing that approximately 10 mg/day of isoflavones is required to inhibit breast cancer occurrence. In addition, flavonoids also influence the epigenetic machinery in breast cancer, with research demonstrating that epigallocatechin, genistein, and resveratrol all inhibited DNA methyltransferase and altered chromatin modification in breast cancer. These flavonoids can induce the expression of different tumor suppressor genes that may contribute to decreasing breast cancer progression and metastasis. Additional studies are required to confirm the contribution of epigenetic modifications by flavonoids to breast cancer prevention. Full article
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
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25 pages, 3859 KiB  
Review
Flavonoids as Anticancer Agents
by Dalia M. Kopustinskiene, Valdas Jakstas, Arunas Savickas and Jurga Bernatoniene
Nutrients 2020, 12(2), 457; https://doi.org/10.3390/nu12020457 - 12 Feb 2020
Cited by 632 | Viewed by 25597
Abstract
Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been [...] Read more.
Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action. Full article
(This article belongs to the Special Issue Flavonoids and Cancer Prevention)
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