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Antioxidants, Phytonutrients and Cancer Risk

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

Deadline for manuscript submissions: closed (25 November 2021) | Viewed by 42289

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Dr. Michele M. Iskandar

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Guest Editor

School of Human Nutrition, McGill University, 21,111 Lakeshore Rd, Ste-Anne-de-Bellevue, Quebec, Canada.
Interests: nutrition and health; phytochemicals; inflammation and oxidative stress; bioavailability; prebiotics and probiotics; gut microbiome

Special Issue Information

Dear Colleagues,

As cancer remains one of the leading causes of death worldwide, the hunt for chemopreventive agents and anticancer drugs to complement existing cancer therapies is the subject of ongoing research. Phytochemicals, naturally occurring compounds from plants, have been shown to exert chemopreventive and chemotherapeutic effects in cell lines, animal models and human studies. Their mechanisms of action have been widely explored and include antioxidant, anti-inflammatory effects, epigenetic regulation, cell cycle regulation, immunomodulation, inhibition of cell proliferation, modulation of cell signaling pathways and modulation of the gut microbiota, to name a few. In this Special Issue of Nutrients entitled “Antioxidants, phytonutrients and cancer risk”, we aim to collect and showcase recent findings on this topic with a multidisciplinary and multifaceted approach, with the objective of advancing knowledge in this area. We therefore welcome the submission of manuscripts describing original research or reviewing the scientific literature on this very challenging topic.

Dr. Michele M. Iskandar
Guest Editor

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Keywords

phytochemicals
phytonutrients
cancer
chemoprevention
antioxidant
anti-inflammatory
anti-tumorigenic

Published Papers (11 papers)

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Research

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14 pages, 14588 KiB

Open AccessArticle

Olive Mill Wastewater Inhibits Growth and Proliferation of Cisplatin- and Gemcitabine-Resistant Bladder Cancer Cells In Vitro by Down-Regulating the Akt/mTOR-Signaling Pathway

by Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Felix K.-H. Chun, Igor Tsaur and Roman A. Blaheta

Nutrients 2022, 14(2), 369; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14020369 - 15 Jan 2022

Cited by 3 | Viewed by 1713

Abstract

Bladder cancer patients whose tumors develop resistance to cisplatin-based chemotherapy often turn to natural, plant-derived products. Beneficial effects have been particularly ascribed to polyphenols, although their therapeutic relevance when resistance has developed is not clear. The present study evaluated the anti-tumor potential of polyphenol-rich olive mill wastewater (OMWW) on chemo-sensitive and cisplatin- and gemcitabine-resistant T24, RT112, and TCCSUP bladder cancer cells in vitro. The cells were treated with different dilutions of OMWW, and tumor growth and clone formation were evaluated. Possible mechanisms of action were investigated by evaluating cell cycle phases and cell cycle-regulating proteins. OMWW profoundly inhibited the growth and proliferation of chemo-sensitive as well as gemcitabine- and cisplatin-resistant bladder cancer cells. Depending on the cell line and on gemcitabine- or cisplatin-resistance, OMWW induced cell cycle arrest at different phases. These differing phase arrests were accompanied by differing alterations in the CDK-cyclin axis. Considerable suppression of the Akt-mTOR pathway by OMWW was observed in all three cell lines. Since OMWW blocks the cell cycle through the manipulation of the cyclin-CDK axis and the deactivation of Akt-mTOR signaling, OMWW could become relevant in supporting bladder cancer therapy. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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13 pages, 586 KiB

Open AccessArticle

The Prognostic Role of Glutathione and Its Related Antioxidant Enzymes in the Recurrence of Hepatocellular Carcinoma

by Yung-Fang Hsiao, Shao-Bin Cheng, Chia-Yu Lai, Hsiao-Tien Liu, Shih-Chien Huang and Yi-Chia Huang

Nutrients 2021, 13(11), 4071; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13114071 - 14 Nov 2021

Cited by 16 | Viewed by 2187

Abstract

The imbalance of high oxidative stress and low antioxidant capacities is thought to be a significant cause of the development and progression of hepatocellular carcinoma (HCC). However, the impact of oxidative stress, glutathione (GSH), and its related antioxidant enzymes on the recurrence of HCC has not been investigated. The purpose of this study was to compare the changes to oxidative stress and GSH-related antioxidant capacities before and after tumor resection in patients with HCC recurrence and non-recurrence. We also evaluated the prognostic significance of GSH and its related enzymes in HCC recurrence. This was a cross-sectional and follow-up study. Ninety-two HCC patients who were going to receive tumor resection were recruited. We followed patients’ recurrence and survival status until the end of the study, and then assigned patients into the recurrent or the non-recurrent group. The tumor recurrence rate was 52.2% during the median follow-up period of 3.0 years. Patients had significantly lower plasma malondialdehyde level, but significantly or slightly higher levels of GSH, glutathione disulfide, trolox equivalent antioxidant capacity, glutathione peroxidase (GPx), and glutathione reductase (GR) activities after tumor resection compared to the respective levels before tumor resection in both recurrent and non-recurrent groups. GSH level in HCC tissue was significantly higher than that in adjacent normal tissue in both recurrent and non-recurrent patients. Decreased plasma GPx (HR = 0.995, p = 0.01) and GR (HR = 0.98, p = 0.04) activities before tumor resection, and the increased change of GPx (post—pre-resection) (HR = 1.004, p = 0.03) activity were significantly associated with the recurrence of HCC. These findings suggest there might be a possible application of GPx or GR as therapeutic targets for reducing HCC recurrence. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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12 pages, 1268 KiB

Open AccessArticle

Association between Dietary Intake of Flavonoids and Cancer Recurrence among Breast Cancer Survivors

by Minjung Cheon, Minsung Chung and Yongsoon Park

Nutrients 2021, 13(9), 3049; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13093049 - 30 Aug 2021

Cited by 4 | Viewed by 2960

Abstract

Intake of flavonoids is associated with the incidence of breast cancer, but the association between the intake of flavonoids and cancer recurrence is unclear. This study aimed to investigate the hypothesis that intake of flavonoids and flavonoid-rich foods is negatively associated with cancer recurrence. Among 572 women who underwent breast cancer surgery, 66 patients had a cancer recurrence. Dietary data were collected using a structured 24-h dietary recall, and intake of flavonoids was calculated based on the Korea Rural Development Administration flavonoid database. Among overweight and obese patients, disease-free survival was associated with intake of flavonoids (p = 0.004) and flavonoid-rich foods (p = 0.003). Intake of flavonoids (hazard ratio (HR) = 0.249, 95% confidence interval (CI): 0.09–0.64) and flavonoid-rich foods (HR = 0.244, 95% CI: 0.09–0.66) was negatively associated with cancer recurrence after adjusting for confounding factors in overweight and obese patients. Consumption of flavonoids and flavonoid-rich foods was lower in overweight and obese patients with cancer recurrence than those without recurrence and in normal-weight patients. This study suggests that intake of flavonoids and flavonoid-rich foods could have beneficial effects on cancer recurrence in overweight and obese breast cancer survivors. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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16 pages, 2792 KiB

Open AccessArticle

FABP7 Facilitates Uptake of Docosahexaenoic Acid in Glioblastoma Neural Stem-like Cells

by Won-Shik Choi, Xia Xu, Susan Goruk, Yixiong Wang, Samir Patel, Michael Chow, Catherine J. Field and Roseline Godbout

Nutrients 2021, 13(8), 2664; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13082664 - 30 Jul 2021

Cited by 8 | Viewed by 3053

Abstract

Glioblastoma (GBM) is an aggressive tumor with a dismal prognosis. Neural stem-like cells contribute to GBM’s poor prognosis by driving drug resistance and maintaining cellular heterogeneity. GBM neural stem-like cells express high levels of brain fatty acid-binding protein (FABP7), which binds to polyunsaturated fatty acids (PUFAs) ω-6 arachidonic acid (AA) and ω-3 docosahexaenoic acid (DHA). Similar to brain, GBM tissue is enriched in AA and DHA. However, DHA levels are considerably lower in GBM tissue compared to adult brain. Therefore, it is possible that increasing DHA content in GBM, particularly in neural stem-like cells, might have therapeutic value. Here, we examine the fatty acid composition of patient-derived GBM neural stem-like cells grown as neurosphere cultures. We also investigate the effect of AA and DHA treatment on the fatty acid profiles of GBM neural stem-like cells with or without FABP7 knockdown. We show that DHA treatment increases DHA levels and the DHA:AA ratio in GBM neural stem-like cells, with FABP7 facilitating the DHA uptake. We also found that an increased uptake of DHA inhibits the migration of GBM neural stem-like cells. Our results suggest that increasing DHA content in the GBM microenvironment may reduce the migration/infiltration of FABP7-expressing neural stem-like cancer cells. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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16 pages, 3731 KiB

Open AccessArticle

Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma

by Aitor Benedicto, Iera Hernandez-Unzueta, Eduardo Sanz and Joana Márquez

Nutrients 2021, 13(2), 686; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020686 - 21 Feb 2021

Cited by 8 | Viewed by 3930

Abstract

Whereas the prevalence of several cancer types is decreasing, skin malignancies are growing more common every year. Malignant melanoma is the most aggressive form of skin cancer with high metastatic capacity. In most cases, malignant melanoma shows acquired therapy resistance. We evaluated the ability of Ocoxin, a natural compound-based antioxidant and anti-inflammatory nutritional complement, to exert an antitumor effect in melanoma. To do so, the cytotoxicity of Ocoxin in a panel of BRAF-mutated murine and human melanoma cell lines was tested alone and in combination with BRAF inhibitor Vemurafenib. Our results revealed a potent cytotoxic effect of Ocoxin against melanoma cells and a synergic effect when combined with Vemurafenib, reducing viability and increasing apoptosis. Besides, Ocoxin interferes with the cell cycle, impairs the inherent and fibroblast-mediated melanoma cell migration, and reduces resistance to BRAF inhibition. Proteomic analysis revealed reduced tumor secretion of inflammatory factors Galectin-1, Osteopontin, CCL5, and CCL9 upon treatment with Ocoxin. Moreover, RNASeq showed that Ocoxin downregulated the cell cycle and proliferation-related genes. In vivo, Ocoxin reduced the number of lung metastasis of YUMM-1.7 melanoma cells. Therefore, Ocoxin arises as a good candidate for clinical trials analyzing the beneficial effects in patients suffering from this cutaneous malignancy. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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18 pages, 3212 KiB

Open AccessArticle

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

by Mohammad Hassan Hodroj, Nour al Hoda Al Bast, Robin I. Taleb, Jamilah Borjac and Sandra Rizk

Nutrients 2020, 12(9), 2629; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12092629 - 28 Aug 2020

Cited by 14 | Viewed by 5414

Abstract

Urtica dioica (UD), commonly known as “stinging nettle”, is a herbaceous flowering plant that is a widely used agent in traditional medicine worldwide. Several formulations of UD leaf extract have been reported to exhibit anti-inflammatory and antioxidant properties, with anticancer potential. The current study investigated the possible anticancer properties of nettle tea, prepared from Urtica dioica leaves, on acute myeloid leukemia (AML) cell lines, and deciphered the underlying molecular mechanisms. Treatment of AML cell lines (U-937 and KG-1) with UD aqueous leaf extract resulted in a dose- and time-dependent inhibition of proliferation, an increase in apoptotic hallmarks such as phosphatidylserine flipping to the outer membrane leaflet, and DNA fragmentation as revealed by cell-death ELISA and cell-cycle analysis assays. Apoptosis induction in U937 cells involves alterations in the expression of Bax and Bcl-2 upon exposure to nettle tea. Furthermore, the chemical composition of UD aqueous extract indicated the presence of multiple chemical agents, such as flavonoids and phenolics, mainly patuletin, m/p-hydroxybenzoic acid, and caffeic acid, among others, to which the pro-apoptotic and anti-tumor effects may be attributed. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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17 pages, 1998 KiB

Open AccessArticle

Vanillin Prevents Doxorubicin-Induced Apoptosis and Oxidative Stress in Rat H9c2 Cardiomyocytes

by Ivana Sirangelo, Luigi Sapio, Angela Ragone, Silvio Naviglio, Clara Iannuzzi, Daniela Barone, Antonio Giordano and Margherita Borriello

Nutrients 2020, 12(8), 2317; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12082317 - 01 Aug 2020

Cited by 26 | Viewed by 4254

Abstract

Doxorubicin (doxo) is an effective anticancer compound in several tumor types. However, as a consequence of oxidative stress induction and ROS overproduction, its high cardiotoxicity demands urgent attention. Vanillin possesses antioxidant, antiproliferative, antidepressant and anti-glycating properties. Therefore, we investigated the potential vanillin protective effects against doxo-induced cardiotoxicity in H9c2 cells. Using multiparametric approach, we demonstrated that vanillin restored both cell viability and damage in response to doxo exposure. Contextually, vanillin decreased sub-G1 appearance and caspase-3 and PARP1 activation, reducing the doxo-related apoptosis induction. From a mechanistic point of view, vanillin hindered doxo-induced ROS accumulation and impaired the ERK phosphorylation. Notably, besides the cardioprotective effects, vanillin did not counteract the doxo effectiveness in osteosarcoma cells. Taken together, our results suggest that vanillin ameliorates doxo-induced toxicity in H9c2 cells, opening new avenues for developing alternative therapeutic approaches to prevent the anthracycline-related cardiotoxicity and to improve the long-term outcome of antineoplastic treatment. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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Review

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15 pages, 1308 KiB

Open AccessReview

The Association between Carotenoids and Head and Neck Cancer Risk

by Adam Brewczyński, Beata Jabłońska, Marek Kentnowski, Sławomir Mrowiec, Krzysztof Składowski and Tomasz Rutkowski

Nutrients 2022, 14(1), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14010088 - 26 Dec 2021

Cited by 9 | Viewed by 3492

Abstract

Head and neck cancer (HNC) includes oral cavity cancer (OCC), pharyngeal cancer (PC), and laryngeal cancer (LC). It is one of the most frequent cancers in the world. Smoking and alcohol consumption are the typical well-known predictors of HNC. Human papillomavirus (HPV) is an increasing etiological factor for oropharyngeal cancer (OPC). Moreover, food and nutrition play an important role in HNC etiology. According to the World Cancer Research Fund and the American Institute for Cancer Research, an intake of non-starchy vegetables and fruits could decrease HNC risk. The carotenoids included in vegetables and fruits are well-known antioxidants which have anti-mutagenic and immune regulatory functions. Numerous studies have shown the relationship between carotenoid intake and a lower HNC risk, but the role of carotenoids in HNC risk is not well defined. The goal of this review is to present the current literature regarding the relationship between various carotenoids and HNC risk. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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22 pages, 4826 KiB

Open AccessReview

Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review

by Ali Qusay Khalid, Saatheeyavaane Bhuvanendran, Kasthuri Bai Magalingam, Premdass Ramdas, Mangala Kumari and Ammu Kutty Radhakrishnan

Nutrients 2021, 13(11), 4056; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13114056 - 12 Nov 2021

Cited by 4 | Viewed by 2801

Abstract

The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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13 pages, 512 KiB

Open AccessReview

Physiological and Immune Functions of Punicalagin

by Eva Venusova, Adriana Kolesarova, Pavel Horky and Petr Slama

Nutrients 2021, 13(7), 2150; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13072150 - 23 Jun 2021

Cited by 35 | Viewed by 4796

Abstract

The aim of this publication is to compile a summary of the findings regarding punicalagin in various tissues described thus far in the literature, with an emphasis on the effect of this substance on immune reactions. Punicalagin (PUN) is an ellagitannin found in the peel of pomegranate (Punica granatum). It is a polyphenol with proven antioxidant, hepatoprotective, anti-atherosclerotic and chemopreventive activities, antiproliferative activity against tumor cells; it inhibits inflammatory pathways and the action of toxic substances, and is highly tolerated. This work describes the source, metabolism, functions and effects of punicalagin, its derivatives and metabolites. Furthermore, its anti-inflammatory and antioxidant effects are described. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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15 pages, 1559 KiB

Open AccessReview

The Immunomodulatory Effects of Honey and Associated Flavonoids in Cancer

by Razan J. Masad, Shoja M. Haneefa, Yassir A. Mohamed, Ashraf Al-Sbiei, Ghada Bashir, Maria J. Fernandez-Cabezudo and Basel K. al-Ramadi

Nutrients 2021, 13(4), 1269; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13041269 - 13 Apr 2021

Cited by 25 | Viewed by 6334

Abstract

Honey has exerted a high impact in the field of alternative medicine over many centuries. In addition to its wound healing, anti-microbial and antioxidant properties, several lines of evidence have highlighted the efficiency of honey and associated bioactive constituents as anti-tumor agents against a range of cancer types. Mechanistically, honey was shown to inhibit cancer cell growth through its pro-apoptotic, anti-proliferative and anti-metastatic effects. However, the potential of honey to regulate anti-tumor immune responses is relatively unexplored. A small number of in vitro and in vivo studies have demonstrated the ability of honey to modulate the immune system by inducing immunostimulatory as well as anti-inflammatory effects. In the present review, we summarize the findings from different studies that aimed to investigate the immunomodulatory properties of honey and its flavonoid components in relation to cancer. While these studies provide promising data, additional research is needed to further elucidate the immunomodulatory properties of honey, and to enable its utilization as an adjuvant therapy in cancer. Full article

(This article belongs to the Special Issue Antioxidants, Phytonutrients and Cancer Risk)

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