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Exploration of Homocysteine Metabolism in Cancer and Petechial Therapeutic Targets

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

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 3076

Special Issue Editors


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Guest Editor
Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
Interests: molecular genetics; genetic engineering; biochemistry; cancer metastasis; targeted therapy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Biomedical and Biotechnological Sciences, University of Catania, 95124 Catania, Italy
Interests: autoimmune diseases; cancer; neurological diseases; pshychiatric diseases; reactive oxygen species; reactive nitrogen species; nitric oxide; hydrogen suflide; carbon monoxide; heme oxygenase

Special Issue Information

Dear Colleagues,

Homocysteine (Hcy) is a non-essential amino acid that is produced through the one-carbon metabolism pathway. This is the only pathway that supplies methyl groups to DNA, RNA, and proteins. One-carbon metabolism via the methionine cycle is essential during nucleotide synthesis, methylation, and reductive metabolism, and this pathway supports the high proliferative rate of cancer cells. In the last two decades, several studies have shown that disruption of this pathway is linked to different systemic diseases, such as cardiovascular disorder, neurodegenerative diseases, type 2 diabetes, etc. However, very few studies have been carried out that show that increased plasma Hcy has also been closely related to cancer. Cancer cells require a constant supply of methionine from external sources (also known as the Hoffman effect), suggesting that possibly cancer cells need increased demand for metabolites derived from the one-carbon metabolism pathway. To understand this fact, we need to decode the metabolites that are generated from this one-carbon metabolism cycle.

We invite researchers to contribute to this Special Issue who are working on the generation and usage of one-carbon units in cancer. Original research articles or review articles on the innovative aspect of the exploration of possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism are welcome.

Dr. Avisek Majumder
Prof. Dr. Ferdinando Nicoletti
Guest Editors

Manuscript Submission Information

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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

  • hyperhomocysteinemia
  • cancer
  • one carbon metabolism
  • homocysteine
  • cancer therapeutics
  • cancer metabolism
  • methionine cycle
  • methylation
  • epigenetics
  • methyl group donor

Published Papers (1 paper)

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Research

29 pages, 6188 KiB  
Article
Flaxseed Increases Animal Lifespan and Reduces Ovarian Cancer Severity by Toxically Augmenting One-Carbon Metabolism
by William C. Weston, Karen H. Hales and Dale B. Hales
Molecules 2021, 26(18), 5674; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26185674 - 18 Sep 2021
Cited by 5 | Viewed by 2413
Abstract
We used an LC-MS/MS metabolomics approach to investigate one-carbon metabolism in the plasma of flaxseed-fed White Leghorn laying hens (aged 3.5 years). In our study, dietary flaxseed (via the activity of a vitamin B6 antagonist known as “1-amino d-proline”) induced at least [...] Read more.
We used an LC-MS/MS metabolomics approach to investigate one-carbon metabolism in the plasma of flaxseed-fed White Leghorn laying hens (aged 3.5 years). In our study, dietary flaxseed (via the activity of a vitamin B6 antagonist known as “1-amino d-proline”) induced at least 15-fold elevated plasma cystathionine. Surprisingly, plasma homocysteine (Hcy) was stable in flaxseed-fed hens despite such highly elevated cystathionine. To explain stable Hcy, our data suggest accelerated Hcy remethylation via BHMT and MS-B12. Also supporting accelerated Hcy remethylation, we observed elevated S-adenosylmethionine (SAM), an elevated SAM:SAH ratio, and elevated methylthioadenosine (MTA), in flaxseed-fed hens. These results suggest that flaxseed increases SAM biosynthesis and possibly increases polyamine biosynthesis. The following endpoint phenotypes were observed in hens consuming flaxseed: decreased physiological aging, increased empirical lifespan, 9–14% reduced body mass, and improved liver function. Overall, we suggest that flaxseed can protect women from ovarian tumor metastasis by decreasing omental adiposity. We also propose that flaxseed protects cancer patients from cancer-associated cachexia by enhancing liver function. Full article
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