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Dietary Bioactive Ingredients in the Modulation of Signaling Pathways in Cancer

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

Deadline for manuscript submissions: closed (15 October 2025) | Viewed by 658

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Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA
Interests: medicinal and pharmaceutical chemistry; bioactivity; natural products; drug discovery; breast and prostate tumors; molecular modeling; molecular cell biology; cancer recurrence; cancer cell motility
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Special Issue Information

Dear Colleagues,

Epidemiological studies have highlighted the role of dietary bioactive ingredients in reducing the incidence of certain malignancies. Examples of validated cancer-modulating effects enabled by dietary bioactive ingredients include the reduced susceptibility of Mediterranean and Southeast Asian populations to certain cancers due to their dietary consumption of olive phenolics and soy isoflavones, respectively. Dietary bioactive ingredients are recognized as being able to directly suppress and prevent cancers or indirectly suppress cancers through crosstalk with the human gut microbiota. Emerging bioinformatic technologies such as RNA and single-cell sequencing show potential in validating the anticancer contributions of bioactive dietary ingredients and aiding in the discovery of more novel cancer-selective targeted mechanistic signaling pathways, which will facilitate their nutraceutical use to achieve improved therapeutic outcomes. For this Special Issue, we welcome submissions highlighting the contribution of dietary bioactive ingredients to cancer prevention and control, as well as their molecular mechanisms.

Prof. Dr. Khalid A. El Sayed
Guest Editor

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Keywords

  • bioactive dietary ingredients
  • cancer prevention
  • cancer progression
  • cancer-targeted pathways
  • nutraceuticals
  • metastasis
  • signaling transduction

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Published Papers (1 paper)

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Research

15 pages, 40390 KB  
Article
Fisetin Inhibits Periodontal Pathogen-Induced EMT in Oral Squamous Cell Carcinoma via the Wnt/β-Catenin Pathway
by Ruoyao Zhang, Hiroki Takigawa, Hugo Maruyama, Takayuki Nambu, Chiho Mashimo and Toshinori Okinaga
Nutrients 2025, 17(22), 3522; https://doi.org/10.3390/nu17223522 - 11 Nov 2025
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Abstract
Objective: Previous reports showed that periodontopathic bacteria induce epithelial–mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Fisetin, a foodborne flavonoid, is reportedly associated with anticancer potential in various carcinogenic processes. This study aimed to elucidate the effects of fisetin on Fusobacterium [...] Read more.
Objective: Previous reports showed that periodontopathic bacteria induce epithelial–mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC). Fisetin, a foodborne flavonoid, is reportedly associated with anticancer potential in various carcinogenic processes. This study aimed to elucidate the effects of fisetin on Fusobacterium nucleatum- and Porphyromonas gingivalis-induced EMT in OSCC cells. Methods: OSCC cells were co-cultured with live and heat-killed forms of F. nucleatum and P. gingivalis. The concentration of fisetin was set at 10 μM. Morphological changes in the OSCC cells were observed under a light microscope. Cell viability was measured using the Cell Counting Kit-8 assay, whereas migration was examined via wound healing. The mRNA expression of EMT-related markers was quantified using quantitative real-time polymerase chain reaction (PCR), and the expression of EMT-related markers and Wnt pathway-associated proteins was examined via Western blotting. Results: At a multiplicity of infection (MOI) of 300:1 for F. nucleatum and 100:1 for P. gingivalis, OSCC cell viability remained unchanged; however, wound closure rates increased significantly relative to the control. Likewise, treatment with fisetin (10 µM) did not materially alter viability; nevertheless, it attenuated promigratory effects induced by heat-killed periodontal pathogens at 3 h and 6 h. The OSCC cells exhibited EMT-like morphological changes after 6 h of co-culture with heat-killed pathogens. Consistently, reverse-transcriptase quantitative PCR and Western blot analyses showed increased expression of TWIST, ZEB1, and N-cadherin, accompanied by decreased E-cadherin expression, which was more pronounced in F. nucleatum than in P. gingivalis. However, fisetin reversed these trends. Moreover, co-culture with heat-killed pathogens markedly elevated β-catenin protein levels. In line with modulation of canonical Wnt/β-catenin signaling, fisetin and a Wnt inhibitor reduced β-catenin expression, whereas co-treatment with a Wnt agonist restored β-catenin levels in the presence of fisetin. Conclusions: Heat-killed F. nucleatum and P. gingivalis induced EMT in OSCC cells, with F. nucleatum exerting the strongest effect. Fisetin suppressed pathogen-driven EMT, at least partly via canonical Wnt/β-catenin signaling, highlighting its potential therapeutic value and warranting further investigation. Full article
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