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New Therapies based on Cancer Metabolic Remodelling

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 20343

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Special Issue Editors

Prof. Dr. Jacinta Serpa

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Guest Editor

1. Chronic Diseases Research Centre (CEDOC), NOVA Medical School, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
2. Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), 1099-023 Lisboa, Portugal
Interests: cancer; metabolism; angiogenesis; cancer therapy

Dr. Sofia C. Nunes

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Guest Editor

CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
Interests: oncobiology; cancer metabolism; chemoresistance; evolutionary biology

Special Issue Information

Dear Colleagues,

Tumor microenvironment (TME) exerts several selective pressures on cancer cells, such as acidosis, hypoxia, or anti-cancer therapies. The cells that are able to adapt upon those stressful conditions will be the carriers of disease progression. Metabolism is the basis of cell survival, and metabolic rewiring is an important requirement in TME adaptive process. Hence, the increasing knowledge of cancer metabolic remodeling is promising to disclose new core targets for the design of more specific and adjusted anti-cancer therapies. The Special Issue "New Therapies Based on Cancer Metabolic Remodeling", in the scope of Molecules MDPI journal, welcomes original research or review articles, covering the aspects of cancer metabolism and the tumor microenvironment related to therapy response and chemoresistance, as well as their potential targeting with new therapies.
We look forward to receiving your papers.

Prof. Jacinta Serpa
Dr. Sofia C. Nunes
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. Molecules is an international peer-reviewed open access semimonthly 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 metabolism
Tumor microenvironment
Chemoresistance
New targets
New drugs
Metabolic remodeling
Targeted therapy

Published Papers (5 papers)

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Research

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11 pages, 1293 KiB

Open AccessArticle

Redox State and Lysosomal Activity in Women with Ovarian Cancer with Tumor Recurrence and Multiorgan Metastasis

by Paweł Sutkowy, Jolanta Czuczejko, Bogdan Małkowski, Karolina Szewczyk-Golec, Rita Łopatto, Marta Maruszak and Alina Woźniak

Molecules 2021, 26(13), 4039; https://doi.org/10.3390/molecules26134039 - 01 Jul 2021

Cited by 4 | Viewed by 1954

Abstract

The aim of the study is to evaluate oxidant–antioxidant balance as well as lysosomal and anti-protease activities in ovarian cancer since it has been emphasized that the crucial inducing factor of carcinogenesis may be reactive oxygen/nitrogen species or, more precisely, oxidative stress-induced inflammation. The study involved 15 women with ovarian cancer, aged 59.9 ± 7.8 years, and 9 healthy women aged 56.3 ± 4.3 years (controls). The study material was venous blood collected from fasting subjects. In erythrocytes, the activities of superoxide dismutase, glutathione peroxidase, and catalase, as well as concentrations of conjugated dienes (CDs) and thiobarbituric acid reactive substances (TBARS), were investigated. CD, TBARS, and vitamins A and E plasma concentrations were also determined. Moreover, total antioxidant capacity and concentrations of 4-hydroxynonenal adducts and 8-iso-prostaglandin F2α, as well as activities of acid phosphatase, arylsulfatase, cathepsin D, and α₁-antitrypsin, were studied in serum. The vitamin E and 8-iso-prostaglandin F2α concentrations as well as arylsulfatase activity were lower in the women with cancer compared to the controls (p = 0.006, p = 0.03, p = 0.001, respectively). In contrast, cathepsin D activity was lower in the controls (p = 0.04). In the peripheral blood of the women with cancer, oxidant–antioxidant and lysosomal disturbances were observed. Full article

(This article belongs to the Special Issue New Therapies based on Cancer Metabolic Remodelling)

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11 pages, 2064 KiB

Open AccessArticle

Design, Synthesis and In-Vitro Biological Evaluation of Antofine and Tylophorine Prodrugs as Hypoxia-Targeted Anticancer Agents

by Ziad Omran, Chris P. Guise, Linwei Chen, Cyril Rauch, Ashraf N. Abdalla, Omeima Abdullah, Ikhlas A. Sindi, Peter M. Fischer, Jeff B. Smaill, Adam V. Patterson, Yuxiu Liu and Qingmin Wang

Molecules 2021, 26(11), 3327; https://doi.org/10.3390/molecules26113327 - 01 Jun 2021

Cited by 3 | Viewed by 3474

Abstract

Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood–brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions. Full article

(This article belongs to the Special Issue New Therapies based on Cancer Metabolic Remodelling)

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Graphical abstract

15 pages, 1910 KiB

Open AccessArticle

The Impact of Olive Oil Compounds on the Metabolic Reprogramming of Cutaneous Melanoma Cell Models

by Cheila Brito, Ana Tomás, Sandra Silva, Maria Rosário Bronze, Ana Teresa Serra and Marta Pojo

Molecules 2021, 26(2), 289; https://doi.org/10.3390/molecules26020289 - 08 Jan 2021

Cited by 7 | Viewed by 2460

Abstract

Cutaneous melanoma is the deadliest type of skin cancer, characterized by a high molecular and metabolic heterogeneity which contributes to therapy resistance. Despite advances in treatment, more efficient therapies are needed. Olive oil compounds have been described as having anti-cancer properties. Here, we clarified the cytotoxic potential of oleic acid, homovanillyl alcohol, and hydroxytyrosol on melanoma cells. Metabolic viability was determined 48 h post treatment of A375 and MNT1 cells. Metabolic gene expression was assessed by qRT-PCR and Mitogen-Activated Protein Kinase (MAPK) activation by Western blot. Hydroxytyrosol treatment (100 and 200 µM) significantly reduced A375 cell viability (p = 0.0249; p < 0.0001) which, based on the expression analysis performed, is more compatible with a predominant glycolytic profile and c-Jun N-terminal kinase (JNK) activation. By contrast, hydroxytyrosol had no effect on MNT1 cell viability, which demonstrates an enhanced oxidative metabolism and extracellular signal-regulated kinase (ERK) activation. This compound triggered cell detoxification and the use of alternative energy sources in A375 cells, inhibiting JNK and ERK pathways. Despite oleic acid and homovanillyl alcohol demonstrating no effect on melanoma cell viability, they influenced the MNT1 glycolytic rate and A375 detoxification mechanisms, respectively. Both compounds suppressed ERK activation in MNT1 cells. The distinct cell responses to olive oil compounds depend on the metabolic and molecular mechanisms preferentially activated. Hydroxytyrosol may have a cytotoxic potential in melanoma cells with predominant glycolytic metabolism and JNK activation. Full article

(This article belongs to the Special Issue New Therapies based on Cancer Metabolic Remodelling)

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Review

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40 pages, 1835 KiB

Open AccessReview

Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy

by Jiaqi Li, Jie Qing Eu, Li Ren Kong, Lingzhi Wang, Yaw Chyn Lim, Boon Cher Goh and Andrea L. A. Wong

Molecules 2020, 25(20), 4831; https://doi.org/10.3390/molecules25204831 - 20 Oct 2020

Cited by 72 | Viewed by 8038

Abstract

Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. There is also emerging evidence regarding the role of stromal components, creating an intricate metabolic network consisting of cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells, and cancer stem cells. This metabolic rewiring and crosstalk with the tumour microenvironment play a key role in cell proliferation, metastasis, and the development of treatment resistance. In this review, we will discuss therapeutic opportunities, which arise from dysregulated metabolism and metabolic crosstalk, highlighting strategies that may aid in the precision targeting of altered tumour metabolism with a focus on combinatorial therapeutic strategies. Full article

(This article belongs to the Special Issue New Therapies based on Cancer Metabolic Remodelling)

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24 pages, 2221 KiB

Open AccessReview

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

by Ana Hipólito, Sofia C. Nunes, João B. Vicente and Jacinta Serpa

Molecules 2020, 25(17), 3984; https://doi.org/10.3390/molecules25173984 - 01 Sep 2020

Cited by 17 | Viewed by 3710

Abstract

Metabolic remodeling is a critical skill of malignant cells, allowing their survival and spread. The metabolic dynamics and adaptation capacity of cancer cells allow them to escape from damaging stimuli, including breakage or cross-links in DNA strands and increased reactive oxygen species (ROS) levels, promoting resistance to currently available therapies, such as alkylating or oxidative agents. Therefore, it is essential to understand how metabolic pathways and the corresponding enzymatic systems can impact on tumor behavior. Cysteine aminotransferase (CAT) per se, as well as a component of the CAT: 3-mercaptopyruvate sulfurtransferase (MST) axis, is pivotal for this metabolic rewiring, constituting a central mechanism in amino acid metabolism and fulfilling the metabolic needs of cancer cells, thereby supplying other different pathways. In this review, we explore the current state-of-art on CAT function and its role on cancer cell metabolic rewiring as MST partner, and its relevance in cancer cells’ fitness. Full article

(This article belongs to the Special Issue New Therapies based on Cancer Metabolic Remodelling)

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