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Lipids as Supporting Therapy in Cancer
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Lipids as Supporting Therapy in Cancer

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

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 12611

Special Issue Editors

Prof. Dr. Massimo Nabissi

E-Mail Website
Guest Editor
1. School of Pharmacy, University of Camerino, 62032 Camerino, Italy
2. Integrative Therapy Discovery Lab, School of Pharmacy, University of Camerino, 62032 Camerino, Italy
Interests: oncology; immunotherapy; cannabinoids; chemotherapy
Special Issues, Collections and Topics in MDPI journals
Dr. Oliviero Marinelli

E-Mail Website
Guest Editor
Immunopathology Laboratory, School of Pharmacy, University of Camerino, 62032 Camerino, Italy
Interests: oncology; immunotherapy; cannabinoids; chemotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The current anticancer chemotherapeutic drugs toxicity and partial efficacy as well as the development of multiple drug resistance are the major problems for some cancer therapies. So, the development of well-tolerated agents with different mode of action on cancer metabolism might be used in combination with chemotherapeutic drugs as an adjuvant therapy. Lipids have been studied as anticancer agents and lipid metabolism is involved in the regulation of many cancers cellular processes such as cell growth, proliferation, survival, apoptosis, inflammation, invasion and drug resistance.  Moreover, since lipids metabolism is modulated by multiple signaling pathways and give rise to different bioactive lipid molecules such as fatty acid, eicosanoids, diacylglycerol and many others, lipids metabolism and its derivates has been subject of intense studies for understanding the underlying mechanisms involved in cancer process regulation. Our issue is dedicated to the improvement of the lipids molecular and metabolic interaction events that contribute to reducing carcinogenesis and the identification of novel lipid-regulating pathways able to interfere with carcinogenesis. Therefore, we invite submissions that cover lipids and lipids-derivates anticancer activities, that accompanies all stages of tumor development. We aim to contribute in the identification of novel compounds and potential adjuvant therapies for reducing cancer progression.  Our Special Issue also aims to publish papers dealing with the molecular basis of lipids interaction with oncogene and tumor suppressor expression, role in cell cycle and cell death regulation, and all molecular pathways involved in anti-cancer approaches.

Prof. Dr. Massimo Nabissi
Dr. Oliviero Marinelli
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. 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

  • lipids
  • anticancer metabolism
  • polyunsaturated fatty acids (PUFA)
  • essential oil
  • Short-chain fatty acids (SCFA)

Published Papers (5 papers)

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Research

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25 pages, 3407 KiB  
Article
Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition
by Catarina M. Morais, Ana M. Cardoso, Ana Rita D. Araújo, Ana Reis, Pedro Domingues, Maria Rosário M. Domingues, Maria C. Pedroso de Lima and Amália S. Jurado
Int. J. Mol. Sci. 2022, 23(21), 13014; https://doi.org/10.3390/ijms232113014 - 27 Oct 2022
Cited by 2 | Viewed by 1855
Abstract
Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work [...] Read more.
Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic. Full article
(This article belongs to the Special Issue Lipids as Supporting Therapy in Cancer)
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13 pages, 1935 KiB  
Article
Conjugation of the 9-kDa Isoform of Granulysin with Liposomes Potentiates Its Cytotoxicity
by Ruth Soler-Agesta, Patricia Guerrero-Ochoa, Joaquín Marco-Brualla, Raquel Ibáñez-Pérez, Isabel Marzo, Luis Martínez-Lostao and Alberto Anel
Int. J. Mol. Sci. 2022, 23(15), 8705; https://doi.org/10.3390/ijms23158705 - 5 Aug 2022
Cited by 1 | Viewed by 1692
Abstract
Nine kDa granulysin (GRNLY) is a human cytolytic protein secreted by cytotoxic T lymphocytes (CTL) and NK cells of the immune system whose demonstrated physiological function is the elimination of bacteria and parasites. In previous studies by our group, the anti-tumor capacity of [...] Read more.
Nine kDa granulysin (GRNLY) is a human cytolytic protein secreted by cytotoxic T lymphocytes (CTL) and NK cells of the immune system whose demonstrated physiological function is the elimination of bacteria and parasites. In previous studies by our group, the anti-tumor capacity of recombinant granulysin was demonstrated, both in vitro and in vivo. In the present work, we developed lipid nanoparticles whose surfaces can bind recombinant granulysin through the formation of a complex of coordination between the histidine tail of the protein and Ni2+ provided by a chelating lipid in the liposome composition and termed them LUV-GRNLY, for granulysin-bound large unilamellar vesicles. The objective of this formulation is to increase the granulysin concentration at the site of contact with the target cell and to increase the cytotoxicity of the administered dose. The results obtained in this work indicate that recombinant granulysin binds to the surface of the liposome with high efficiency and that its cytotoxicity is significantly increased when it is in association with liposomes. In addition, it has been demonstrated that the main mechanism of death induced by both granulysin and LUV-GRNLY is apoptosis. Jurkat-shBak cells are resistant to GRNLY and also to LUV-GRNLY, showing that LUV-GRNLY uses the mitochondrial apoptotic pathway to induce cell death. On the other hand, we show that LUV-GRNLY induces the expression of the pro-apoptotic members of the Bcl-2 family Bim and especially PUMA, although it also induced the expression of anti-apoptotic Bcl-xL. In conclusion, we demonstrate that binding of GRNLY to the surfaces of liposomes clearly augments its cytotoxic potential, with cell death executed mainly by the mitochondrial apoptotic pathway. Full article
(This article belongs to the Special Issue Lipids as Supporting Therapy in Cancer)
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20 pages, 3099 KiB  
Article
Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins
by Mayra Montecillo-Aguado, Belen Tirado-Rodriguez, Gabriela Antonio-Andres, Mario Morales-Martinez, Zhen Tong, Jun Yang, Bruce D. Hammock, Rogelio Hernandez-Pando and Sara Huerta-Yepez
Int. J. Mol. Sci. 2022, 23(11), 6179; https://doi.org/10.3390/ijms23116179 - 31 May 2022
Cited by 12 | Viewed by 2781
Abstract
Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several [...] Read more.
Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-β. Full article
(This article belongs to the Special Issue Lipids as Supporting Therapy in Cancer)
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Review

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28 pages, 1803 KiB  
Review
Artificial and Naturally Derived Phospholipidic Bilayers as Smart Coatings of Solid-State Nanoparticles: Current Works and Perspectives in Cancer Therapy
by Nicolò Maria Percivalle, Marco Carofiglio, Marzia Conte, Giada Rosso, Alessandro Bentivogli, Giulia Mesiano, Veronica Vighetto and Valentina Cauda
Int. J. Mol. Sci. 2022, 23(24), 15815; https://doi.org/10.3390/ijms232415815 - 13 Dec 2022
Cited by 3 | Viewed by 2284
Abstract
Recent advances in nanomedicine toward cancer treatment have considered exploiting liposomes and extracellular vesicles as effective cargos to deliver therapeutic agents to tumor cells. Meanwhile, solid-state nanoparticles are continuing to attract interest for their great medical potential thanks to their countless properties and [...] Read more.
Recent advances in nanomedicine toward cancer treatment have considered exploiting liposomes and extracellular vesicles as effective cargos to deliver therapeutic agents to tumor cells. Meanwhile, solid-state nanoparticles are continuing to attract interest for their great medical potential thanks to their countless properties and possible applications. However, possible drawbacks arising from the use of nanoparticles in nanomedicine, such as the nonspecific uptake of these materials in healthy organs, their aggregation in biological environments and their possible immunogenicity, must be taken into account. Considering these limitations and the intrinsic capability of phospholipidic bilayers to act as a biocompatible shield, their exploitation for effectively encasing solid-state nanoparticles seems a promising strategy to broaden the frontiers of cancer nanomedicine, also providing the possibility to engineer the lipid bilayers to further enhance the therapeutic potential of such nanotools. This work aims to give a comprehensive overview of the latest developments in the use of artificial liposomes and naturally derived extracellular vesicles for the coating of solid-state nanoparticles for cancer treatment, starting from in vitro works until the up-to-date advances and current limitations of these nanopharmaceutics in clinical applications, passing through in vivo and 3D cultures studies. Full article
(This article belongs to the Special Issue Lipids as Supporting Therapy in Cancer)
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21 pages, 1776 KiB  
Review
Critical Review on Fatty Acid-Based Food and Nutraceuticals as Supporting Therapy in Cancer
by Carla Ferreri, Anna Sansone, Chryssostomos Chatgilialoglu, Rosaria Ferreri, Javier Amézaga, Mercedes Caro Burgos, Sara Arranz and Itziar Tueros
Int. J. Mol. Sci. 2022, 23(11), 6030; https://doi.org/10.3390/ijms23116030 - 27 May 2022
Cited by 7 | Viewed by 3257
Abstract
Fatty acids have an important place in both biological and nutritional contexts and, from a clinical point of view, they have known consequences for diseases’ onset and development, including cancer. The use of fatty acid-based food and nutraceuticals to support cancer therapy is [...] Read more.
Fatty acids have an important place in both biological and nutritional contexts and, from a clinical point of view, they have known consequences for diseases’ onset and development, including cancer. The use of fatty acid-based food and nutraceuticals to support cancer therapy is a multidisciplinary subject, involving molecular and clinical research. Knowledge regarding polyunsaturated fatty acids essentiality/oxidizability and the role of lipogenesis-desaturase pathways for cell growth, as well as oxidative reactivity in cancer cells, are discussed, since they can drive the choice of fatty acids using their multiple roles to support antitumoral drug activity. The central role of membrane fatty acid composition is highlighted for the application of membrane lipid therapy. As fatty acids are also known as biomarkers of cancer onset and progression, the personalization of the fatty acid-based therapy is also possible, taking into account other important factors such as formulation, bioavailability and the distribution of the supplementation. A holistic approach emerges combining nutra- and pharma-strategies in an appropriate manner, to develop further knowledge and applications in cancer therapy. Full article
(This article belongs to the Special Issue Lipids as Supporting Therapy in Cancer)
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