Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Roles of Phytochemicals in Cancer Prevention and Therapeutics

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Related Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 25407

Share This Special Issue

Special Issue Editor

Dr. Daniel Gabriel Pons

E-Mail Website
Guest Editor

1. Multidisciplinar Group in Traslational Oncology (GMOT), Balearic Islands University (UIB), 07122 Palma, Spain
2. Balearic Islands Health Research Institute (IdISBa), 07010 Palma, Spain
Interests: oxidative stress; estrogen; phytoestrogens; cancer cells; personalized treatment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Interest in the use of phytochemicals for the prevention and treatment of cancer is growing year by year. Recent studies have demonstrated the impact that this type of molecules can have on mammal cells. On the one hand, it is known that certain phytochemicals at low or moderate concentrations can delay the onset of cancer due to their antioxidant, anti-inflammatory, and even antimicrobial properties. However, when cancer is already established, it is precisely these properties of these compounds that can lead to the appearance of a subpopulation of cancer cells that are more resistant to cell death. On the other hand, higher concentrations of these compounds can cause drastic changes in the physiology of cancer cells, causing a decrease in their growth and proliferation and even causing their death. Therefore, the study of the effects of phytochemicals is of great interest because of the dual effects they may have on both normal cells and cancer cells.

Dr. Daniel Gabriel Pons
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
cancer prevention
cancer therapeutics
oxidative stress
inflammation
energetic metabolism

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Related Special Issue

Roles of Phytochemicals in Cancer Prevention and Therapeutics: 2nd Edition in International Journal of Molecular Sciences

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research, Review

5 pages, 197 KiB

Open AccessEditorial

Roles of Phytochemicals in Cancer Prevention and Therapeutics

by Daniel Gabriel Pons

Int. J. Mol. Sci. 2024, 25(10), 5450; https://doi.org/10.3390/ijms25105450 - 17 May 2024

Cited by 1 | Viewed by 1118

Abstract

This Special Issue focused on the importance of phytochemicals for their use in the prevention and treatment of cancer [...] Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

Research

Jump to: Editorial, Review

21 pages, 4504 KiB

Open AccessArticle

Apoptosis Induction in HepG2 and HCT116 Cells by a Novel Quercetin-Zinc (II) Complex: Enhanced Absorption of Quercetin and Zinc (II)

by Mizuki Nakamura, Daigo Urakawa, Ziyu He, Isao Akagi, De-Xing Hou and Kozue Sakao

Int. J. Mol. Sci. 2023, 24(24), 17457; https://doi.org/10.3390/ijms242417457 - 14 Dec 2023

Cited by 3 | Viewed by 1684

Abstract

Quercetin forms complexes with various metals due to its structural attributes. It predominantly exhibits chelating activity at the 3-hydroxy/4-carbonyl group. Previously, coordination in synthetically obtained quercetin–zinc (II) complexes has been limited to this group. However, the expanded coordination observed in quercetin–iron complexes has opened avenues for diverse applications. Thus, synthesizing novel quercetin–zinc complexes with different coordination positions is a significant advance. In our study, we not only synthesized and comprehensively characterized a new quercetin–zinc (II) complex, Zn-Q, but also evaluated the structure and bioactivity of chelate complexes (Q+Zn) derived from co-treatment in cell culture mediums. The structure of the new compound Zn-Q was comprehensively characterized using 1D ¹H and 2D correlation spectroscopy (COSY), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV-Vis), electrospray ionization mass spectrometer (ESI-MS), and X-ray diffraction analysis (XRD) analysis. Subcellular localization and absorption of these zinc (II) complexes were determined using the ZnAF-2 DA zinc ion fluorescence probe. Throughout the experiments, both Zn-Q and Q+Zn exhibited significant antioxidant, cell growth inhibitory, and anticancer effects in HepG2 and HCT116 cells, with Zn-Q showing the highest potential for inducing apoptosis via the caspase pathway. Tracking intracellular zinc complex absorption using zinc fluorescent probes revealed zinc (II) localization around the cell nucleus. Interestingly, there was a proportional increase in intracellular quercetin absorption in conjunction with zinc (II) uptake. Our research highlights the advantages of quercetin complexation with zinc (II): enhanced anticancer efficacy compared to the parent compound and improved bioavailability of both quercetin and zinc (II). Notably, our findings, which include enhanced intracellular uptake of both quercetin and zinc (II) upon complex formation and its implications in apoptosis, contribute significantly to the understanding of metal–polyphenol complexes. Moving forward, comprehensive functional assessments and insights into its mechanism of action, supported by animal studies, are anticipated. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Figure 1

18 pages, 20347 KiB

Open AccessArticle

Butein Inhibits Cell Growth by Blocking the IL-6/IL-6Rα Interaction in Human Ovarian Cancer and by Regulation of the IL-6/STAT3/FoxO3a Pathway

by Sun-Ae Park, Young Ju Seo, Lee Kyung Kim, Hee Jung Kim, Kee Dong Yoon and Tae-Hwe Heo

Int. J. Mol. Sci. 2023, 24(7), 6038; https://doi.org/10.3390/ijms24076038 - 23 Mar 2023

Cited by 7 | Viewed by 2190

Abstract

Butea monosperma (Fabaceae) has been used in traditional Indian medicine to treat a variety of ailments, including abdominal tumors. We aimed to investigate the anti-IL-6 activity of butein in ovarian cancer and elucidate the underlying molecular mechanisms. Butein was isolated and identified from B. monosperma flowers, and the inhibition of IL-6 signaling was investigated using the HEK-Blue™ IL-6 cell line. The surface plasmon resonance assay was used to estimate the binding of butein to IL-6, IL-6Rα, and gp130. After treatment with butein, ovarian cancer cell migration, apoptosis, and tumor growth inhibition were evaluated in vitro and in vivo. Furthermore, we used STAT3 siRNA to identify the mechanistic effects of butein on the IL-6/STAT3/FoxO3a pathway. Butein suppressed downstream signal transduction through higher binding affinity to IL-6. In ovarian cancer, butein inhibited cell proliferation, migration, and invasion, and induced cell cycle arrest and apoptosis. In addition, it decreased the growth of ovarian cancer cells in xenograft tumor models. Butein inhibited STAT3 phosphorylation and induced FoxO3a accumulation in the nucleus by inhibiting IL-6 signaling. The anticancer activity of butein was mediated by blocking the IL-6/IL-6Rα interaction and suppressing IL-6 bioactivity via interfering with the IL-6/STAT3/FoxO3a pathway. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Graphical abstract

29 pages, 2531 KiB

Open AccessArticle

Phytochemical Profiling of Extracts from Rare Potentilla Species and Evaluation of Their Anticancer Potential

by Daniel Augustynowicz, Marta Kinga Lemieszek, Jakub Władysław Strawa, Adrian Wiater and Michał Tomczyk

Int. J. Mol. Sci. 2023, 24(5), 4836; https://doi.org/10.3390/ijms24054836 - 2 Mar 2023

Cited by 5 | Viewed by 2579

Abstract

Despite the common use of Potentilla L. species (Rosaceae) as herbal medicines, a number of species still remain unexplored. Thus, the present study is a continuation of a study evaluating the phytochemical and biological profiles of aqueous acetone extracts from selected Potentilla species. Altogether, 10 aqueous acetone extracts were obtained from the aerial parts of P. aurea (PAU7), P. erecta (PER7), P. hyparctica (PHY7), P. megalantha (PME7), P. nepalensis (PNE7), P. pensylvanica (PPE7), P. pulcherrima (PPU7), P. rigoi (PRI7), and P. thuringiaca (PTH7), leaves of P. fruticosa (PFR7), as well as from the underground parts of P. alba (PAL7r) and P. erecta (PER7r). The phytochemical evaluation consisted of selected colourimetric methods, including total phenolic (TPC), tannin (TTC), proanthocyanidin (TPrC), phenolic acid (TPAC), and flavonoid (TFC) contents, as well as determination of the qualitative secondary metabolite composition by the employment of LC–HRMS (liquid chromatography–high-resolution mass spectrometry) analysis. The biological assessment included an evaluation of the cytotoxicity and antiproliferative properties of the extracts against human colon epithelial cell line CCD841 CoN and human colon adenocarcinoma cell line LS180. The highest TPC, TTC, and TPAC were found in PER7r (326.28 and 269.79 mg gallic acid equivalents (GAE)/g extract and 263.54 mg caffeic acid equivalents (CAE)/g extract, respectively). The highest TPrC was found in PAL7r (72.63 mg catechin equivalents (CE)/g extract), and the highest TFC was found in PHY7 (113.29 mg rutin equivalents (RE)/g extract). The LC–HRMS analysis showed the presence of a total of 198 compounds, including agrimoniin, pedunculagin, astragalin, ellagic acid, and tiliroside. An examination of the anticancer properties revealed the highest decrease in colon cancer cell viability in response to PAL7r (IC₅₀ = 82 µg/mL), while the strongest antiproliferative effect was observed in LS180 treated with PFR7 (IC₅₀ = 50 µg/mL) and PAL7r (IC₅₀ = 52 µg/mL). An LDH (lactate dehydrogenase) assay revealed that most of the extracts were not cytotoxic against colon epithelial cells. At the same time, the tested extracts for the whole range of concentrations damaged the membranes of colon cancer cells. The highest cytotoxicity was observed for PAL7r, which in concentrations from 25 to 250 µg/mL increased LDH levels by 145.7% and 479.0%, respectively. The previously and currently obtained results indicated that some aqueous acetone extracts from Potentilla species have anticancer potential and thus encourage further studies in order to develop a new efficient and safe therapeutic strategy for people who have been threatened by or suffered from colon cancer. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Figure 1

17 pages, 29858 KiB

Open AccessArticle

A Mulberry Diels-Alder-Type Adduct, Kuwanon M, Triggers Apoptosis and Paraptosis of Lung Cancer Cells through Inducing Endoplasmic Reticulum Stress

by Mengjiao Ma, Xiaoyi Luan, Hao Zheng, Xiaoning Wang, Shuqi Wang, Tao Shen and Dongmei Ren

Int. J. Mol. Sci. 2023, 24(2), 1015; https://doi.org/10.3390/ijms24021015 - 5 Jan 2023

Cited by 12 | Viewed by 2430

Abstract

The mulberry tree (Morus alba) has been cultivated in China for thousands of years. Mulberry Diels-Alder-type adducts (MDAAs) are characteristic constituents of the genus Morus. The unique structure and diverse bioactivities of MDAAs have attracted the attention of researchers. Kuwanon M (KWM) is an MDAA isolated from the root bark of Morus alba. This research reports the growth inhibitory effects of KWM on human lung cancer cells and its possible mechanism. In A549 and NCI-H292 cells, KWM treatment induced suppression of cell proliferation and migration. The appearance of chromatin condensation, phosphatidyl serine exposure and caspase cleavage indicated the arising of apoptosis. The loss of mitochondrial membrane potential (MMP), release of cytochrome c and dysregulation of Bax/Bcl-2 demonstrated that the KWM-induced apoptosis was through the mitochondrial pathway. Paraptosis was simultaneously detected under KWM treatment, as evidenced by the exhibition of cytoplasmic vacuolation, down-regulation of Alix and up-regulation of endoplasmic reticulum (ER) stress-related proteins. Mechanistically, ER stress induced activation of unfolded protein response (UPR) pathways and activation of the MAPK (JNK and ERK) pathway, all of which were critical for KWM-induced apoptosis and paraptosis. These findings suggested the possibility that KWM might be considered as a potential lung cancer therapeutic agent. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Figure 1

16 pages, 3148 KiB

Open AccessArticle

Elevation of Anticancer Drug Toxicity by Caffeine in Spheroid Model of Human Lung Adenocarcinoma A549 Cells Mediated by Reduction in Claudin-2 and Nrf2 Expression

by Hiroaki Eguchi, Riho Kimura, Saki Onuma, Ayaka Ito, Yaqing Yu, Yuta Yoshino, Toshiyuki Matsunaga, Satoshi Endo and Akira Ikari

Int. J. Mol. Sci. 2022, 23(24), 15447; https://doi.org/10.3390/ijms232415447 - 7 Dec 2022

Cited by 9 | Viewed by 2156

Abstract

Claudin-2 (CLDN2), a component of tight junctions, is abnormally expressed in human lung adenocarcinoma tissue. CLDN2 contributes to chemoresistance in human lung adenocarcinoma-derived A549 cells, and it may be a target for cancer therapy. Here, we found that coffee ingredients, namely caffeine and theobromine, decreased the protein level of CLDN2 in human lung adenocarcinoma-derived A549 cells. In contrast, other components, such as theophylline and chlorogenic acid, had no effect. These results indicate that the 7-methyl group in methylxanthines may play a key role in the reduction in CLDN2 expression. The caffeine-induced reduction in the CLDN2 protein was inhibited by chloroquine, a lysosome inhibitor. In a protein-stability assay using cycloheximide, CLDN2 protein levels decreased faster in caffeine-treated cells than in vehicle-treated cells. These results suggest that caffeine accelerates the lysosomal degradation of CLDN2. The accumulation and cytotoxicity of doxorubicin were dose-dependently increased, which was exaggerated by caffeine but not by theophylline in spheroids. Caffeine decreased nuclear factor-erythroid 2-related factor 2 (Nrf2) levels without affecting hypoxia-inducible factor-1α levels. Furthermore, caffeine decreased the expression of Nrf2-targeted genes. The effects of caffeine on CLDN2 expression and anticancer-drug-induced toxicity were also observed in lung adenocarcinoma RERF-LC-MS cells. We suggest that caffeine enhances doxorubicin-induced toxicity in A549 spheroids mediated by the reduction in CLDN2 and Nrf2 expression. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Figure 1

19 pages, 4147 KiB

Open AccessArticle

High Concentrations of Genistein Decrease Cell Viability Depending on Oxidative Stress and Inflammation in Colon Cancer Cell Lines

by Marina Alorda-Clara, Margalida Torrens-Mas, Pere Miquel Morla-Barcelo, Pilar Roca, Jorge Sastre-Serra, Daniel Gabriel Pons and Jordi Oliver

Int. J. Mol. Sci. 2022, 23(14), 7526; https://doi.org/10.3390/ijms23147526 - 7 Jul 2022

Cited by 16 | Viewed by 2742

Abstract

Genistein could play a crucial role in modulating three closely linked physiological processes altered during cancer: oxidative stress, mitochondrial biogenesis, and inflammation. However, genistein’s role in colorectal cancer remains unclear. We aimed to determine genistein’s effects in two colon cancer cells: HT29 and SW620, primary and metastatic cancer cells, respectively. After genistein treatment for 48 h, cell viability and hydrogen peroxide (H₂O₂) production were studied. The cell cycle was studied by flow cytometry, mRNA and protein levels were analyzed by RT-qPCR and Western blot, respectively, and finally, cytoskeleton remodeling and NF-κB translocation were determined by confocal microscopy. Genistein 100 µM decreased cell viability and produced G₂/M arrest, increased H₂O₂, and produced filopodia in SW620 cells. In HT29 cells, genistein produced an increase of cell death, H₂O₂ production, and in the number of stress fibers. In HT29 cells, mitochondrial biogenesis was increased, however, in SW620 cells, it was decreased. Finally, the expression of inflammation-related genes increased in both cell lines, being greater in SW620 cells, where NF-κB translocation to the nucleus was higher. These results indicate that high concentrations of genistein could increase oxidative stress and inflammation in colon cancer cells and, ultimately, decrease cell viability. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

14 pages, 1229 KiB

Open AccessReview

Dietary Isothiocyanates: Novel Insights into the Potential for Cancer Prevention and Therapy

by Guanqiong Na, Canxia He, Shunxi Zhang, Sicong Tian, Yongping Bao and Yujuan Shan

Int. J. Mol. Sci. 2023, 24(3), 1962; https://doi.org/10.3390/ijms24031962 - 19 Jan 2023

Cited by 18 | Viewed by 5122

Abstract

Diet plays an important role in health. A high intake of plant chemicals such as glucosinolates/isothiocyanates can promote optimal health and decrease the risk of cancer. Recent research has discovered more novel mechanisms of action for the effects of isothiocyanates including the modulation of tumor microenvironment, the inhibition of the self-renewal of stem cells, the rearrangement of multiple pathways of energy metabolism, the modulation of microbiota, and protection against Helicobacter pylori. However, the hormetic/biphasic effects of isothiocyanates may make the recommendations complicated. Isothiocyanates possess potent anti-cancer activities based on up-to-date evidence from in vitro and in vivo studies. The nature of hormesis suggests that the benefits or risks of isothiocyanates largely depend on the dose and endpoint of interest. Isothiocyanates are a promising class of cancer-preventative phytochemicals, but researchers should be aware of the potential adverse (and hormetic) effects. In the authors’ opinion, dietary isothiocyanates are better used as adjunctive treatments in combination with known anti-cancer drugs. The application of nano-formulations and the delivery of isothiocyanates are also discussed in this review. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Figure 1

35 pages, 1866 KiB

Open AccessReview

Why Do Dietary Flavonoids Have a Promising Effect as Enhancers of Anthracyclines? Hydroxyl Substituents, Bioavailability and Biological Activity

by Aleksandra Golonko, Adam Jan Olichwier, Renata Swislocka, Lukasz Szczerbinski and Włodzimierz Lewandowski

Int. J. Mol. Sci. 2023, 24(1), 391; https://doi.org/10.3390/ijms24010391 - 26 Dec 2022

Cited by 9 | Viewed by 4327

Abstract

Anthracyclines currently play a key role in the treatment of many cancers, but the limiting factor of their use is the widespread phenomenon of drug resistance and untargeted toxicity. Flavonoids have pleiotropic, beneficial effects on human health that, apart from antioxidant activity, are currently considered small molecules—starting structures for drug development and enhancers of conventional therapeutics. This paper is a review of the current and most important data on the participation of a selected series of flavonoids: chrysin, apigenin, kaempferol, quercetin and myricetin, which differ in the presence of an additional hydroxyl group, in the formation of a synergistic effect with anthracycline antibiotics. The review includes a characterization of the mechanism of action of flavonoids, as well as insight into the physicochemical parameters determining their bioavailability in vitro. The crosstalk between flavonoids and the molecular activity of anthracyclines discussed in the article covers the most important common areas of action, such as (1) disruption of DNA integrity (genotoxic effect), (2) modulation of antioxidant response pathways, and (3) inhibition of the activity of membrane proteins responsible for the active transport of drugs and xenobiotics. The increase in knowledge about the relationship between the molecular structure of flavonoids and their biological effect makes it possible to more effectively search for derivatives with a synergistic effect with anthracyclines and to develop better therapeutic strategies in the treatment of cancer. Full article

(This article belongs to the Special Issue Roles of Phytochemicals in Cancer Prevention and Therapeutics)

► Show Figures

Journal Menu

Journal Browser

Roles of Phytochemicals in Cancer Prevention and Therapeutics

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (9 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI