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Anticancer Activities of Dietary Phytochemicals
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Anticancer Activities of Dietary Phytochemicals

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

Deadline for manuscript submissions: 25 August 2024 | Viewed by 15078

Special Issue Editors

Prof. Dr. Ching-Hsein Chen

E-Mail Website
Guest Editor
Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi City 600, Taiwan
Interests: apoptosis; autophagy; free radical biology and medicine; cancer chemoprevention; anticancer research; preventive medicine; natural product activities; disease prevention research
Prof. Dr. Yi-Wen Liu

E-Mail Website
Guest Editor
Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi City 600, Taiwan
Interests: anticancer research; anti-inflammation study; gene regulation; cancer biomarker

Special Issue Information

Dear Colleagues,

Cancer, also known as malignant tumors, refers to the abnormal proliferation of cells, and these proliferating cells may invade other parts of the body. In humans, more than one hundred types of cancer are currently known. Many cancers can be prevented by eating more fruits, vegetables, and whole grains. The treatment of cancer, whether it is chemotherapy, surgery, or radiotherapy, is a huge burden on the body. Once malignant metastasis occurs, it becomes challenging to achieve a complete cure regardless of the method employed. Therefore, the treatment of cancer remains a significant challenge for human beings.

The aim of this Special Issue is to provide research articles that elucidate the anticancer activity of dietary phytochemicals, with a special emphasis on cancer treatment, cancer prevention, the research and development of dietary phytochemicals as anticancer molecules, their synergistic effects with the clinical chemotherapy drugs for anticancer treatment, and the mechanisms of food phytochemicals in combating cancer. Research articles covering the effects of crude extracts, extracted fractions, and small molecular, macromolecular, and/or pure compounds, as well as their derivatives, with a focus on their application in the control of various human cancer diseases and their benefits for human health, are also welcome.

Prof. Dr. Ching-Hsein Chen
Prof. Dr. Yi-Wen Liu
Guest Editors

Manuscript Submission Information

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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

  • phytochemicals
  • dietary
  • nutrients
  • bioactivities
  • isolation and identification
  • cancers
  • cancer cytotoxicity
  • cancer therapy
  • cancer prevention
  • cancer metastasis

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Published Papers (10 papers)

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Research

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11 pages, 4111 KiB  
Article
Fractionated Leaf Extracts of Ocimum gratissimum Inhibit the Proliferation and Induce Apoptosis of A549 Lung Adenocarcinoma Cells
by Rachael M. Curtis, Heng-Shan Wang, Xuan Luo, Erika B. Dugo, Jacqueline J. Stevens and Paul B. Tchounwou
Nutrients 2024, 16(16), 2737; https://doi.org/10.3390/nu16162737 (registering DOI) - 16 Aug 2024
Abstract
Previous in vitro studies in our laboratory demonstrated that ethyl acetate (P2) and water- soluble (PS/PT1) fractionated leaf extracts of Ocimum gratissimum inhibit the proliferation of prostate cancer cells. It has been reported that the crude aqueous extract induces apoptosis in [...] Read more.
Previous in vitro studies in our laboratory demonstrated that ethyl acetate (P2) and water- soluble (PS/PT1) fractionated leaf extracts of Ocimum gratissimum inhibit the proliferation of prostate cancer cells. It has been reported that the crude aqueous extract induces apoptosis in lung adenocarcinoma cells; however, the efficacy of the fractionated extracts against these cells remains unclear. In the present study, we hypothesized that the ability of the fractionated extracts to inhibit proliferation and induce apoptosis is associated with the activation of pro-apoptotic proteins and induction of DNA condensation in A549 cells. Ocimum gratissimum was cultivated and its leaves were harvested, extracted, and fractionated to produce fractions P2 and PS/PT1. Anti-proliferative activity was assessed by direct cell count. For morphological characterization of apoptosis, 4′,6-diamidino-2-phenylindole staining was employed. Western blot analysis was performed to evaluate the apoptotic activity of the fractionated extracts. In data generated from anti-proliferation studies, P2 significantly inhibited cell proliferation in a concentration-dependent manner; PS/PT1 elicited a decrease in the viability of cells, occurring at 500 µg/mL. 4′,6-diamidino-2-phenylindole staining revealed the induction of apoptosis, as evidenced by the formation of apoptotic bodies. Increased levels of pro-apoptotic proteins were observed as the concentrations of the fractionated extracts increased. These results suggest that fractionated leaf extracts of Ocimum gratissimum inhibit the proliferation and induce apoptosis of A549 cells. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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21 pages, 2280 KiB  
Article
Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention
by Álvaro Pérez-Valero, Patricia Magadán-Corpas, Suhui Ye, Juan Serna-Diestro, Sandra Sordon, Ewa Huszcza, Jarosław Popłoński, Claudio J. Villar and Felipe Lombó
Nutrients 2024, 16(8), 1161; https://doi.org/10.3390/nu16081161 - 13 Apr 2024
Cited by 2 | Viewed by 1413
Abstract
Colorectal cancer stands as the third most prevalent form of cancer worldwide, with a notable increase in incidence in Western countries, mainly attributable to unhealthy dietary habits and other factors, such as smoking or reduced physical activity. Greater consumption of vegetables and fruits [...] Read more.
Colorectal cancer stands as the third most prevalent form of cancer worldwide, with a notable increase in incidence in Western countries, mainly attributable to unhealthy dietary habits and other factors, such as smoking or reduced physical activity. Greater consumption of vegetables and fruits has been associated with a lower incidence of colorectal cancer, which is attributed to their high content of fiber and bioactive compounds, such as flavonoids. In this study, we have tested the flavonoids quercetin, luteolin, and xanthohumol as potential antitumor agents in an animal model of colorectal cancer induced by azoxymethane and dodecyl sodium sulphate. Forty rats were divided into four cohorts: Cohort 1 (control cohort), Cohort 2 (quercetin cohort), Cohort 3 (luteolin cohort), and Cohort 4 (xanthohumol cohort). These flavonoids were administered intraperitoneally to evaluate their antitumor potential as pharmaceutical agents. At the end of the experiment, after euthanasia, different physical parameters and the intestinal microbiota populations were analyzed. Luteolin was effective in significantly reducing the number of tumors compared to the control cohort. Furthermore, the main significant differences at the microbiota level were observed between the control cohort and the cohort treated with luteolin, which experienced a significant reduction in the abundance of genera associated with disease or inflammatory conditions, such as Clostridia UCG-014 or Turicibacter. On the other hand, genera associated with a healthy state, such as Muribaculum, showed a significant increase in the luteolin cohort. These results underline the anti-colorectal cancer potential of luteolin, manifested through a modulation of the intestinal microbiota and a reduction in the number of tumors. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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13 pages, 5952 KiB  
Article
Amurensin G Sensitized Cholangiocarcinoma to the Anti-Cancer Effect of Gemcitabine via the Downregulation of Cancer Stem-like Properties
by Yun-Jung Na, Hong Kyu Lee and Kyung-Chul Choi
Nutrients 2024, 16(1), 73; https://doi.org/10.3390/nu16010073 - 25 Dec 2023
Cited by 1 | Viewed by 1207
Abstract
Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with a high mortality rate and refractoriness to chemotherapy. Gemcitabine is an anti-cancer chemotherapeutic agent used for CCA, but the efficacy of gemcitabine in CCA treatment is limited, due to the acquisition of chemoresistance. The [...] Read more.
Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with a high mortality rate and refractoriness to chemotherapy. Gemcitabine is an anti-cancer chemotherapeutic agent used for CCA, but the efficacy of gemcitabine in CCA treatment is limited, due to the acquisition of chemoresistance. The present study evaluated the chemosensitizing effects of Amurensin G (AMG), a natural sirtuin-1 inhibitor derived from Vitis amurensis, in the SNU-478 CCA cells. Treatment with AMG decreased the SNU-478 cell viability and the colony formation ability. Annexin V/ Propidium iodide staining showed that the AMG increased apoptotic death. In addition, AMG downregulated anti-apoptotic Bcl-2 expression, while upregulating pro-apoptotic cleaved caspase-3 expression. Treatment with AMG decreased the migratory ability of the cells in a wound healing assay and transwell migration assay. It was observed that AMG decreased the gemcitabine-induced increase in CD44highCD24highCD133high cell populations, and the expression of the Sox-2 protein was decreased by AMG treatment. Co-treatment of AMG with gemcitabine significantly enhanced the production of reactive oxygen species, as observed through mitochondrial superoxide staining, which might be associated with the downregulation of the Sirt1/Nrf2 pathway by AMG. These results indicate that AMG enhances the chemotherapeutic ability of gemcitabine by downregulating cancer stem-like properties in CCA cells. Hence, a combination therapy of AMG with gemcitabine may be an attractive therapeutic strategy for cholangiocarcinoma. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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13 pages, 3689 KiB  
Article
Drastic Synergy of Lovastatin and Antrodia camphorata Extract Combination against PC3 Androgen-Refractory Prostate Cancer Cells, Accompanied by AXL and Stemness Molecules Inhibition
by Chih-Jung Yao, Chia-Lun Chang, Ming-Hung Hu, Chien-Huang Liao, Gi-Ming Lai, Tzeon-Jye Chiou, Hsien-Ling Ho, Hui-Ching Kuo, Ya-Yu Yang, Jacqueline Whang-Peng and Shuang-En Chuang
Nutrients 2023, 15(21), 4493; https://doi.org/10.3390/nu15214493 - 24 Oct 2023
Viewed by 1357
Abstract
Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death in males worldwide. Early-stage PC patients can benefit from surgical, radiation, and hormonal therapies; however, once the tumor transitions to an androgen-refractory state, the efficacy [...] Read more.
Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death in males worldwide. Early-stage PC patients can benefit from surgical, radiation, and hormonal therapies; however, once the tumor transitions to an androgen-refractory state, the efficacy of treatments diminishes considerably. Recently, the exploration of natural products, particularly dietary phytochemicals, has intensified in response to addressing this prevailing medical challenge. In this study, we uncovered a synergistic effect from combinatorial treatment with lovastatin (an active component in red yeast rice) and Antrodia camphorata (AC, a folk mushroom) extract against PC3 human androgen-refractory PC cells. This combinatorial modality resulted in cell cycle arrest at the G0/G1 phase and induced apoptosis, accompanied by a marked reduction in molecules responsible for cellular proliferation (p-Rb/Rb, Cyclin A, Cyclin D1, and CDK1), aggressiveness (AXL, p-AKT, and survivin), and stemness (SIRT1, Notch1, and c-Myc). In contrast, treatment with either AC or lovastatin alone only exerted limited impacts on the cell cycle, apoptosis, and the aforementioned signaling molecules. Notably, significant reductions in canonical PC stemness markers (CD44 and CD133) were observed in lovastatin/AC-treated PC3 cells. Furthermore, lovastatin and AC have been individually examined for their anti-PC properties. Our findings elucidate a pioneering discovery in the synergistic combinatorial efficacy of AC and clinically viable concentrations of lovastatin on PC3 PC cells, offering novel insights into improving the therapeutic effects of dietary natural products for future strategic design of therapeutics against androgen-refractory prostate cancer. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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12 pages, 2170 KiB  
Article
Molecular Evidence of Breast Cancer Cell Proliferation Inhibition by a Combination of Selected Qatari Medicinal Plants Crude Extracts
by Nouralhuda Alateyah, Mohammed Alsafran, Kamal Usman and Allal Ouhtit
Nutrients 2023, 15(19), 4276; https://doi.org/10.3390/nu15194276 - 7 Oct 2023
Viewed by 1680
Abstract
Breast cancer (BC) is the most common malignancy, and conventional medicine has failed to establish efficient treatment modalities. Conventional medicine failed due to lack of knowledge of the mechanisms that underpin the onset and metastasis of tumors, as well as resistance to treatment [...] Read more.
Breast cancer (BC) is the most common malignancy, and conventional medicine has failed to establish efficient treatment modalities. Conventional medicine failed due to lack of knowledge of the mechanisms that underpin the onset and metastasis of tumors, as well as resistance to treatment regimen. However, Complementary and Alternative medicine (CAM) modalities are currently drawing the attention of both the public and health professionals. Our study examined the effect of a super-combination (SC) of crude extracts, which were isolated from three selected Qatari medicinal plants, on the proliferation, motility and death of BC cells. Our results revealed that SC attenuated cell growth and caused the cell death of MDA-MB-231 cancer cells when compared to human normal neonatal fibroblast cells. On the other hand, functional assays showed that SC reduced BC cell migration and invasion, respectively. SC-inhibited cell cycle and SC-regulated apoptosis was most likely mediated by p53/p21 pathway and p53-regulated Bax/BCL-2/Caspace-3 pathway. Our ongoing experiments aim to validate these in vitro findings in vivo using a BC-Xenograft mouse model. These findings support our hypothesis that SC inhibited BC cell proliferation and induced apoptosis. These findings lay the foundation for further experiments, aiming to validate SC as an effective chemoprevention and/or chemotherapeutic strategy that can ultimately pave the way towards translational research/clinical trials for the eradication of BC. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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14 pages, 4755 KiB  
Article
Hibiscus Anthocyanins Extracts Induce Apoptosis by Activating AMP-Activated Protein Kinase in Human Colorectal Cancer Cells
by Ming-Chang Tsai, Ching-Chun Chen, Tsui-Hwa Tseng, Yun-Ching Chang, Yi-Jie Lin, I-Ning Tsai, Chi-Chih Wang and Chau-Jong Wang
Nutrients 2023, 15(18), 3972; https://doi.org/10.3390/nu15183972 - 14 Sep 2023
Cited by 4 | Viewed by 1478
Abstract
Apoptosis, a programmed cell death process preventing cancer development, can be evaded by cancer cells. AMP-activated protein kinase (AMPK) regulates energy levels and is a key research topic in cancer prevention and treatment. Some bioactive components of Hibiscus sabdariffa L. (HAs), including anthocyanins, [...] Read more.
Apoptosis, a programmed cell death process preventing cancer development, can be evaded by cancer cells. AMP-activated protein kinase (AMPK) regulates energy levels and is a key research topic in cancer prevention and treatment. Some bioactive components of Hibiscus sabdariffa L. (HAs), including anthocyanins, have potential anticancer properties. Our study investigated the in vitro cytotoxic potential and mode of action of HAs extracts containing anthocyanins in colorectal cancer cells. The results showed that Hibiscus anthocyanin-rich extracts induced apoptosis in human colorectal cancer cells through the activation of multiple signaling pathways of AMPK. We observed the dose–response and time-dependent induction of apoptosis with HAs. Subsequently, the activation of Fas-mediated proteins triggered apoptotic pathways associated with Fas-mediated apoptosis-related proteins, including caspase-8/tBid. This caused the release of cytochrome C from the mitochondria, resulting in caspase-3 cleavage and apoptosis activation in intestinal cancer cells. These data elucidate the relationship between Has’ regulation of apoptosis-related proteins in colorectal cancer cells and apoptotic pathways. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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31 pages, 1953 KiB  
Review
The Anticancer Effects and Therapeutic Potential of Kaempferol in Triple-Negative Breast Cancer
by Sukhmandeep Kaur, Patricia Mendonca and Karam F. A. Soliman
Nutrients 2024, 16(15), 2392; https://doi.org/10.3390/nu16152392 - 23 Jul 2024
Viewed by 1235
Abstract
Breast cancer is the second-leading cause of cancer death among women in the United States. Triple-negative breast cancer (TNBC), a subtype of breast cancer, is an aggressive phenotype that lacks estrogen (ER), progesterone (PR), and human epidermal growth (HER-2) receptors, which is challenging [...] Read more.
Breast cancer is the second-leading cause of cancer death among women in the United States. Triple-negative breast cancer (TNBC), a subtype of breast cancer, is an aggressive phenotype that lacks estrogen (ER), progesterone (PR), and human epidermal growth (HER-2) receptors, which is challenging to treat with standardized hormonal therapy. Kaempferol is a natural flavonoid with antioxidant, anti-inflammatory, neuroprotective, and anticancer effects. Besides anti-tumorigenic, antiproliferative, and apoptotic effects, kaempferol protects non-cancerous cells. Kaempferol showed anti-breast cancer effects by inducing DNA damage and increasing caspase 3, caspase 9, and pAMT expression, modifying ROS production by Nrf2 modulation, inducing apoptosis by increasing cleaved PARP and Bax and downregulating Bcl-2 expression, inducing cell cycle arrest at the G2/M phase; inhibiting immune evasion by modulating the JAK-STAT3 pathway; and inhibiting the angiogenic and metastatic potential of tumors by downregulating MMP-3 and MMP-9 levels. Kaempferol holds promise for boosting the efficacy of anticancer agents, complementing their effects, or reversing developed chemoresistance. Exploring novel TNBC molecular targets with kaempferol could elucidate its mechanisms and identify strategies to overcome limitations for clinical application. This review summarizes the latest research on kaempferol’s potential as an anti-TNBC agent, highlighting promising but underexplored molecular pathways and delivery challenges that warrant further investigation to achieve successful clinical translation. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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36 pages, 3266 KiB  
Review
Therapeutic Effects of Natural Products on Liver Cancer and Their Potential Mechanisms
by Jinhong Guo, Wenjie Yan, Hao Duan, Diandian Wang, Yaxi Zhou, Duo Feng, Yue Zheng, Shiqi Zhou, Gaigai Liu and Xia Qin
Nutrients 2024, 16(11), 1642; https://doi.org/10.3390/nu16111642 - 27 May 2024
Viewed by 1421
Abstract
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due [...] Read more.
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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30 pages, 2483 KiB  
Review
Organosulfur Compounds in Colorectal Cancer Prevention and Progression
by Patrick L. McAlpine, Javier Fernández, Claudio J. Villar and Felipe Lombó
Nutrients 2024, 16(6), 802; https://doi.org/10.3390/nu16060802 - 11 Mar 2024
Viewed by 1838
Abstract
This work represents an overview of the current investigations involving organosulfur compounds and colorectal cancer. The molecules discussed in this review have been investigated regarding their impact on colorectal cancer directly, at the in vitro, in vivo, and clinical stages. Organosulfur compounds may [...] Read more.
This work represents an overview of the current investigations involving organosulfur compounds and colorectal cancer. The molecules discussed in this review have been investigated regarding their impact on colorectal cancer directly, at the in vitro, in vivo, and clinical stages. Organosulfur compounds may have indirect effects on colorectal cancer, such as due to their modulating effects on the intestinal microbiota or their positive effects on intestinal mucosal health. Here, we focus on their direct effects via the repression of multidrug resistance proteins, triggering of apoptosis (via the inhibition of histone deacetylases, increases in reactive oxygen species, p53 activation, β-catenin inhibition, damage in the mitochondrial membrane, etc.), activation of TGF-β, binding to tubulin, inhibition of angiogenesis and metastasis mechanisms, and inhibition of cancer stem cells, among others. In general, the interesting positive effects of these nutraceuticals in in vitro tests must be further analyzed with more in vivo models before conducting clinical trials. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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23 pages, 1211 KiB  
Review
Histone Acyl Code in Precision Oncology: Mechanistic Insights from Dietary and Metabolic Factors
by Sultan Neja, Wan Mohaiza Dashwood, Roderick H. Dashwood and Praveen Rajendran
Nutrients 2024, 16(3), 396; https://doi.org/10.3390/nu16030396 - 30 Jan 2024
Viewed by 2339
Abstract
Cancer etiology involves complex interactions between genetic and non-genetic factors, with epigenetic mechanisms serving as key regulators at multiple stages of pathogenesis. Poor dietary habits contribute to cancer predisposition by impacting DNA methylation patterns, non-coding RNA expression, and histone epigenetic landscapes. Histone post-translational [...] Read more.
Cancer etiology involves complex interactions between genetic and non-genetic factors, with epigenetic mechanisms serving as key regulators at multiple stages of pathogenesis. Poor dietary habits contribute to cancer predisposition by impacting DNA methylation patterns, non-coding RNA expression, and histone epigenetic landscapes. Histone post-translational modifications (PTMs), including acyl marks, act as a molecular code and play a crucial role in translating changes in cellular metabolism into enduring patterns of gene expression. As cancer cells undergo metabolic reprogramming to support rapid growth and proliferation, nuanced roles have emerged for dietary- and metabolism-derived histone acylation changes in cancer progression. Specific types and mechanisms of histone acylation, beyond the standard acetylation marks, shed light on how dietary metabolites reshape the gut microbiome, influencing the dynamics of histone acyl repertoires. Given the reversible nature of histone PTMs, the corresponding acyl readers, writers, and erasers are discussed in this review in the context of cancer prevention and treatment. The evolving ‘acyl code’ provides for improved biomarker assessment and clinical validation in cancer diagnosis and prognosis. Full article
(This article belongs to the Special Issue Anticancer Activities of Dietary Phytochemicals)
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