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Biomolecules
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Chemopreventive and Therapeutic Potential of Phytochemicals and Their Analogs against...
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Chemopreventive and Therapeutic Potential of Phytochemicals and Their Analogs against Cancer

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 8255

Special Issue Editors

Prof. Dr. Dietrich Büsselberg

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Guest Editor
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar (Medbay), Qatar Foundation, Education City, Doha P.O. Box 24144, Qatar
Interests: tumor biology; metal toxicity; cellular pain modulation; anti-cancer drugs; natural compounds; phytochemicals
Special Issues, Collections and Topics in MDPI journals
Dr. Samson Mathews Samuel

E-Mail Website
Guest Editor
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar (Medbay), Qatar Foundation, Education City, Doha P.O. Box 24144, Qatar
Interests: angiogenesis; autophagy; breast cancer; cancer (glucose) metabolism; cancer stem cells; diabetes; epithelial-mesenchymal-epithelial transition (EMT/MET); endoplasmic reticulum (ER) stress; metformin; therapeutic resistance; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Peter Kubatka

E-Mail Website
Guest Editor
European Association for Predictive, Preventive and Personalised Medicine, EPMA, 1160 Brussels, Belgium
Interests: cancer, chemoprevention; treatment, animal models; plant functional foods; phytochemicals; cell signaling; epigenetics of cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As per the data from World Health Organization (WHO), cancers remain a leading cause of death and accounted for nearly 10 million deaths in 2020 alone, contributing to an excessive social and economic burden around the globe. Unarguably, both cancer research and modern medicine have made significant advancements in predicting cancer risk, early detection, and diagnosis. Additionally, focused/personalized treatment of different cancers has helped effectively treat cancers, improve the prognosis and quality of life of affected individuals and decrease cancer-related mortality. Notably, 25–28% of modern medicines used to treat various diseases (including several efficacious anticancer drugs that can suppress the initiation, progression, metastatic spread, and relapse of cancers) are naturally sourced or plant-based compounds/derivatives or their potent structural analogs. These phytochemicals target neoplasticity-triggering mechanisms (such as DNA damage, epigenetic modifications, metabolic alterations, chronic inflammation, interactions between aberrant molecular pathways, inhibition of apoptosis, epithelial–mesenchymal transition, invasion, and metastasis) and their related molecular pathways.

Unfortunately, modern medicine is short of new and targeted therapeutic approaches. At the same time, there remains an unmet need to develop cancer prevention strategies and improve treatment strategies to benefit those already affected. Using ‘naturally’ occurring reliable drugs combined with conventional anticancer treatment approaches (surgery, chemo- and/or radiotherapy) could help overcome some of the challenges currently faced in cancer therapeutics (such as acquired drug resistance, cancer stem cells, metastasis, and cancer relapse). Additionally, modern medicine is fast embracing the need for preventive, personalized, precision medicine (3P medicine), and drugs tailored to treat patients on a case-by-case basis are becoming increasingly important.

As a follow up of our successful Special Issue in Biomolecules, entitled “Plant-Derived Natural Compounds in the Management of Cancer: Significance and Challenges”, this Special Issue focuses on the potential and efficacy of naturally derived substances (phytochemicals) and their structural analogs in preventing different cancers and in cancer therapy. We invite original research articles and reviews on phytochemicals and structural analogs in cancer chemoprevention and therapeutics. The topics include, but are not limited to: (1) novel strategies for the extraction, (2) purification and characterization of natural compounds with anticancer activity; (3) novel methodological approaches to enhance the bioavailability of phytochemicals; (4) in-vitro- and in-vivo-based cancer models that evaluate various therapeutic targets of phytochemicals on various aspects of cancer treatment; and (5) clinical investigations into the role of the phytochemical/derivatives on cancer risk, treatment, and survival. Please note that manuscripts on crude extracts without identified active ingredients are not encouraged and cannot be considered for publication as per journal policy.

Prof. Dr. Dietrich Büsselberg
Dr. Samson Mathews Samuel
Prof. Dr. Peter Kubatka
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. Biomolecules is an international peer-reviewed open access monthly 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 2700 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

  • cancer
  • cancer chemoprevention
  • cancer relapse
  • cancer stem cells
  • drug design and delivery
  • drug re-purposing
  • drug resistance
  • epithelial-mesenchymal transition (emt)
  • natural substances
  • oncology
  • oxidative stress/reactive oxygen species
  • phytochemicals
  • structural analogs (phytochemicals)
  • therapeutic resistance
  • tumor metabolism
  • tumor microenvironment

Published Papers (4 papers)

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Research

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11 pages, 1771 KiB  
Article
Improvement of the Physicochemical Limitations of Rhapontigenin, a Cytotoxic Analogue of Resveratrol against Colon Cancer
by Silvia Navarro-Orcajada, Francisco José Vidal-Sánchez, Irene Conesa, Adrián Matencio and José Manuel López-Nicolás
Biomolecules 2023, 13(8), 1270; https://doi.org/10.3390/biom13081270 - 20 Aug 2023
Viewed by 1069
Abstract
It has been argued that methoxylated stilbenes are better candidates for oral administration than hydroxylated stilbenes, including resveratrol, as they share many biological activities but have better bioavailability. By contrast, they have a disadvantage to consider, i.e., their lower hydrophilic character that leads [...] Read more.
It has been argued that methoxylated stilbenes are better candidates for oral administration than hydroxylated stilbenes, including resveratrol, as they share many biological activities but have better bioavailability. By contrast, they have a disadvantage to consider, i.e., their lower hydrophilic character that leads to precipitation issues in the final product. In this work, we analysed and compared the growth inhibition of colorectal cancer cells of the methoxylated stilbene rhapontigenin and some analogues and overcame potential problems in the development of fortified products by designing inclusion complexes. Among several cyclodextrins, we found the one that best fit the molecule by physicochemical and bioinformatics assays. The stoichiometry and the encapsulation constants with natural and modified cyclodextrins were determined by fluorescence spectroscopy. The most promising complexes were analysed at different temperature and pH conditions, determining the thermodynamic parameters, to discover the optimal conditions for the preparation and storage of the products. The results showed that rhapontigenin solubility and stability were significantly improved, achieving a sevenfold increase in water solubility and maintaining more than 73% of the stilbene after three months. These findings could be of great interest for industries that aim to deliver novel bioactive compounds with higher solubility and lower degradation. Full article
(This article belongs to the Special Issue Chemopreventive and Therapeutic Potential of Phytochemicals and Their Analogs against Cancer)
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17 pages, 6777 KiB  
Article
Bicalutamide Anticancer Activity Enhancement by Formulation of Soluble Inclusion Complexes with Cyclodextrins
by Federica De Gaetano, Maria Chiara Cristiano, Donatella Paolino, Consuelo Celesti, Daniela Iannazzo, Venerando Pistarà, Nunzio Iraci and Cinzia Anna Ventura
Biomolecules 2022, 12(11), 1716; https://doi.org/10.3390/biom12111716 - 19 Nov 2022
Cited by 13 | Viewed by 1721
Abstract
Bicalutamide (BCL) is a nonsteroidal antiandrogen drug that represents an alternative to castration in the treatment of prostate cancer, due to its relatively long half-life and tolerable side effects. However, it possesses a very low water solubility that can affect its oral bioavailability. [...] Read more.
Bicalutamide (BCL) is a nonsteroidal antiandrogen drug that represents an alternative to castration in the treatment of prostate cancer, due to its relatively long half-life and tolerable side effects. However, it possesses a very low water solubility that can affect its oral bioavailability. In this work, we developed inclusion complexes of BCL with the highly soluble hydroxypropyl-β-cyclodextrin (HP-β-CyD) and sulfobutylether-β-cyclodextrin (SBE-β-CyD) to increase the water solubility and anticancer activity of BCL. The inclusion complexes were prepared using the freeze-drying method and were then characterized in a solid state via differential scanning calorimetry and X-ray analysis and in solution via phase-solubility studies and UV-vis and NMR spectroscopy. The BCL/HP-β-CyD and BCL/SBE-β-CyD inclusion complexes were amorphous and rapidly dissolved in water. Both the 1H-NMR spectra and molecular modeling studies confirmed the penetration of the 2-(trifluoromethyl)benzonitrile ring of BCL within the cavity of both cyclodextrins (CyDs). Due to the consistent improvement of the water solubility of BCL, the inclusion complexes showed higher antiproliferative activity toward the human prostate androgen-independent cell lines, DU-145 and PC-3, with respect to free BCL. These results demonstrate the ability of HP-β-CyD and SBE-β-CyD to complex BCL, permitting the realization of liquid formulations with potentially high oral bioavailability and/or possible parenteral administration. Full article
(This article belongs to the Special Issue Chemopreventive and Therapeutic Potential of Phytochemicals and Their Analogs against Cancer)
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Review

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14 pages, 1924 KiB  
Review
Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer
by Mariafrancesca Hyeraci, Elena Sofia Papanikolau, Marta Grimaldi, Francesco Ricci, Sabatino Pallotta, Rosanna Monetta, Ylenia Aura Minafò, Giovanni Di Lella, Giovanna Galdo, Damiano Abeni, Luca Fania and Elena Dellambra
Biomolecules 2023, 13(7), 1067; https://doi.org/10.3390/biom13071067 - 02 Jul 2023
Cited by 3 | Viewed by 2420
Abstract
Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. [...] Read more.
Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC. Given the individual and social burdens of skin cancers, performing an adequate prevention is needed. Ultraviolet (UV) ray exposure is one of the main risk factors for skin cancer. Thus, the first-choice prevention strategy is represented by photoprotection that can be both topical and systemic. The latter consists of the oral administration of molecules which protect human skin against the damaging effects of UV rays, acting through antioxidant, anti-inflammatory, or immunomodulator mechanisms. Although several compounds are commonly used for photoprotection, only a few molecules have demonstrated their effectiveness in clinical trials and have been included in international guidelines for NMSC prevention (i.e., nicotinamide and retinoids). Moreover, none of them have been demonstrated as able to prevent MM. Clinical and preclinical data regarding the most common compounds used for systemic photoprotection are reported in this review, with a focus on the main mechanisms involved in their photoprotective properties. Full article
(This article belongs to the Special Issue Chemopreventive and Therapeutic Potential of Phytochemicals and Their Analogs against Cancer)
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26 pages, 2794 KiB  
Review
Potential Treatment Options for Neuroblastoma with Polyphenols through Anti-Proliferative and Apoptotic Mechanisms
by Aisha Kafoud, Zoya Salahuddin, Raghad Sabaawi Ibrahim, Reem Al-Janahi, Alena Mazurakova, Peter Kubatka and Dietrich Büsselberg
Biomolecules 2023, 13(3), 563; https://doi.org/10.3390/biom13030563 - 20 Mar 2023
Cited by 2 | Viewed by 2301
Abstract
Neuroblastoma (NB) is an extracranial tumor of the peripheral nervous system arising from neural crest cells. It is the most common malignancy in infants and the most common extracranial solid tumor in children. The current treatment for high-risk NB involves chemotherapy and surgical [...] Read more.
Neuroblastoma (NB) is an extracranial tumor of the peripheral nervous system arising from neural crest cells. It is the most common malignancy in infants and the most common extracranial solid tumor in children. The current treatment for high-risk NB involves chemotherapy and surgical resection followed by high-dose chemotherapy with autologous stem-cell rescue and radiation treatment. However, those with high-risk NB are susceptible to relapse and the long-term side effects of standard chemotherapy. Polyphenols, including the sub-class of flavonoids, contain more than one aromatic ring with hydroxyl groups. The literature demonstrates their utility in inducing the apoptosis of neuroblastoma cells, mostly in vitro and some in vivo. This review explores the use of various polyphenols outlined in primary studies, underlines the pathways involved in apoptotic activity, and discusses the dosage and delivery of these polyphenols. Primary studies were obtained from multiple databases with search the terms “neuroblastoma”, “flavonoid”, and “apoptosis”. The in vitro studies showed that polyphenols exert an apoptotic effect on several NB cell lines. These polyphenols include apigenin, genistein, didymin, rutin, quercetin, curcumin, resveratrol, butein, bisphenols, and various plant extracts. The mechanisms of the therapeutic effects include calpain-dependent pathways, receptor-mediated apoptosis, and, notably, and most frequently, mitochondrial apoptosis pathways, including the mitochondrial proteins Bax and Bcl-2. Overall, polyphenols demonstrate potency in decreasing NB proliferation and inducing apoptosis, indicating significant potential for further in vivo research. Full article
(This article belongs to the Special Issue Chemopreventive and Therapeutic Potential of Phytochemicals and Their Analogs against Cancer)
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