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Special Issue "Current and Future Cancer Chemoprevention Strategies, Volume II"

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 10 December 2023 | Viewed by 4586

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Dr. Juan F. Santibanez

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Department of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Interests: oncology; tumor progression; chemotherapy; inflammation; cellular senescence
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Dr. César A. Echeverría
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Molecular Biology Laboratory, Faculty of Medicine, University of Atacama, Atacama, Chile
Interests: biologia molecular; fisiopatologia
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Dr. Victor Hugo Villar

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Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK
Interests: cancer metabolism; mTORC1 signaling; glutamine metabolism; hepatocellular carcinoma
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Special Issue Information

Dear Colleagues,

We are pleased to announce the new Special Issue for Pharmaceutics entitled "Current and Future Cancer Chemoprevention Strategies, Volume II."

The increasing understanding of cancer pathobiology has shown how to develop molecular approaches to treating neoplasm and decreasing mortality rates. These advances have also influenced active chemoprevention development to promote cancer prevention and development, reduce cancer incidence or counter disease progression, and cancer recurrence after surgery.

Chemoprevention includes the use of natural, synthetic, or biological agents with the aim, at a molecular level, to reverse, suppress, or prevent either the initial phases of carcinogenesis or the progression of premalignant cells to the invasive disease stage. Understanding chemopreventive agents' molecular mechanisms will shed light on preventing carcinogenesis and new therapeutic strategies’ compounds with potential clinical applications.

For this Special Issue on "Current and future cancer chemoprevention strategies", we encourage authors to submit their original research or review articles that bring new pieces of evidence or synthesis of the most recent and breakthrough data in the field of cancer chemoprevention. Topics include, but are not limited to: inorganic and organic compounds; nano-compounds; natural compounds; plant extracts; hormonal chemopreventive agents; diet-related agents; medication/pharmacological drugs; repurposing drugs.

Dr. Juan Santibanez
Dr. César A. A. Echeverría
Dr. Victor Hugo Villar
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. Pharmaceutics 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 2600 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

chemoprevention
cancer
cell death
metabolism
cell invasion
metastasis

Published Papers (4 papers)

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Research

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Open AccessArticle

Antimetastatic Properties of Prodigiosin and the BH3-Mimetic Obatoclax (GX15-070) in Melanoma

Margarita Espona-Fiedler

Pilar Manuel-Manresa

Cristina Benítez-García

and

Pharmaceutics 2023, 15(1), 97; https://doi.org/10.3390/pharmaceutics15010097 - 28 Dec 2022

Viewed by 1019

Abstract

Metastasis is the primary cause of death in cancer patients. Many current chemotherapeutic agents only show cytotoxic, but not antimetastatic properties. This leads to a reduction in tumor size, but allows cancer cells to disseminate, which ultimately causes patient death. Therefore, novel anticancer compounds with both effects need to be developed. In this work, we analyze the antimetastatic properties of prodigiosin and obatoclax (GX15-070), anticancer drugs of the Prodiginines (PGs) family. We studied PGs’ effects on cellular adhesion and morphology in the human primary and metastatic melanoma cell lines, SK-MEL-28 and SK-MEL-5, and in the murine melanoma cell line, B16F10A. Cell adhesion sharply decreased in the treated cells, and this was accompanied by a reduction in filopodia protrusions and a significant decrease in the number of focal-adhesion structures. Moreover, cell migration was assessed through the wound-healing assay and cell motility was severely inhibited after 24 h of treatment. To elucidate the molecular mechanisms involved, changes in metastasis-related genes were analyzed through a gene-expression array. Key genes related to cellular invasion, migration and chemoresistance were significantly down-regulated. Finally, an in vivo model of melanoma-induced lung metastasis was established and significant differences in lung tumors were observed in the obatoclax-treated mice. Altogether, these results describe, in depth, PGs’ cellular antimetastatic effects and identify in vivo antimetastatic properties of Obatoclax. Full article

(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies, Volume II)

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Open AccessArticle

Suppressing of Src–Hic-5–JNK–AKT Signaling Reduced GAPDH Expression for Preventing the Progression of HuCCT1 Cholangiocarcinoma

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Pharmaceutics 2022, 14(12), 2698; https://doi.org/10.3390/pharmaceutics14122698 - 02 Dec 2022

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Abstract

Cholangiocarcinoma (CCA) is a malignant neoplasm of the bile ducts, being the second most common type of cancer in the liver, and most patients are diagnosed at a late stage with poor prognosis. Targeted therapy aiming at receptors tyrosine kinases (RTKs) such as c-Met or EGFR have been developed but with unsatisfactory outcomes. In our recent report, we found several oncogenic molecules downstream of RTKs, including hydrogen peroxide clone-5 (Hic-5), Src, AKT and JNK, were elevated in tissues of a significant portion of metastatic CCAs. By inhibitor studies and a knockdown approach, these molecules were found to be within the same signal cascade responsible for the migration of HuCCT1 cells, a conventionally used CCA cell line. Herein, we also found Src inhibitor dasatinib and Hic-5 siRNA corporately suppressed HuCCT1 cell invasion. Moreover, dasatinib inhibited the progression of the HuCCT1 tumor on SCID mice skin coupled with decreasing the expression of Hic-5 and EGFR and the activities of Src, AKT and JNK. In addition, we found a glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and several cytoskeletal molecules such as tubulin and cofilin were dramatically decreased after a long-term treatment of the HuCCT1 tumor with a high dose of dasatinib. Specifically, GAPDH was shown to be a downstream effector of the Hic-5/Src/AKT cascade involved in HuCCT1 cell migration. On the other hand, TFK1, another CCA cell line without Hic-5 expression, exhibited very low motility, whereas an ectopic Hic-5 expression enhanced the activation of Src and AKT and marginally increased TFK1 migration. In the future, it is tempting to investigate whether cotargeting Src, Hic-5 and/or GAPDH is efficient for preventing CCA progression in future clinical trials. Full article

(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies, Volume II)

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Open AccessArticle

Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation

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Pharmaceutics 2022, 14(12), 2600; https://doi.org/10.3390/pharmaceutics14122600 - 25 Nov 2022

Cited by 2 | Viewed by 1126

Abstract

Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC₅₀ values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations. Full article

(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies, Volume II)

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Open AccessFeature PaperReview

Chemopreventive and Anticancer Role of Resveratrol against Oral Squamous Cell Carcinoma

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Pharmaceutics 2023, 15(1), 275; https://doi.org/10.3390/pharmaceutics15010275 - 13 Jan 2023

Cited by 2 | Viewed by 1073

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevailing and aggressive head and neck cancers, featuring high morbidity and mortality. The available conventional treatments suffer from several adverse effects and are often inefficient in terms of their survival rates. Thus, seeking novel therapeutic agents and adjuvants is of the utmost importance for modern society. Natural polyphenolic compounds have recently emerged as promising chemopreventive and anticancer agents. Specifically, the natural compound resveratrol (RSV) has recently gained momentum for this purpose. RSV is useful for treating OSCC due to its antiproliferative, antimetastatic, and proapoptotic effects. Additionally, RSV acts against tumor cells while synergically cooperating with chemotherapeutics, overcoming drug resistance phenomena. Despite these wide-spectrum effects, there are few specific investigations regarding RSV’s effects against OSCC animal models that consider different routes and vehicles for the administration of RSV. Interestingly, an injectable RSV-loaded liposome-based formulation was proven to be effective against both in vitro and in vivo OSCC models, demonstrating that the development of RSV-loaded drug delivery systems for systemic and/or loco-regional applications may be the turning point in oral cancer treatment, leading to benefits from both RSV’s properties as well as from targeted delivery. Given these premises, this review offers a comprehensive overview of the in vitro and in vivo effects of RSV and its main derivative, polydatin (PD), against OSCC-related cell lines and animal models, aiming to guide the scientific community in regard to RSV and PD use in the treatment of oral precancerous and cancerous lesions. Full article

(This article belongs to the Special Issue Current and Future Cancer Chemoprevention Strategies, Volume II)

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Special Issue "Current and Future Cancer Chemoprevention Strategies, Volume II"

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