The effects of fructose and metabolic inhibition on hepatocellular carcinoma

Dewdney, Brittany, Alanzay, Mohammed, Gillman, Rhys, Walker, Sarah, Wankell, Miriam, Qiao, Liang, George, Jacob, Roberts, Alex, and Hebbard, Lionel (2020) The effects of fructose and metabolic inhibition on hepatocellular carcinoma. Scientific Reports, 10. 16769.

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Abstract

Hepatocellular carcinoma is rapidly becoming one of the leading causes of cancer-related deaths, largely due to the increasing incidence of non-alcoholic fatty liver disease. This in part may be attributed to Westernised diets high in fructose sugar. While many studies have shown the effects of fructose on inducing metabolic-related liver diseases, little research has investigated the effects of fructose sugar on liver cancer metabolism. The present study aimed to examine the metabolic effects of fructose on hepatocellular carcinoma growth in vitro and in vivo. Fructose sugar was found to reduce cell growth in vitro, and caused alterations in the expression of enzymes involved in the serine-glycine synthesis and pentose phosphate pathways. These biosynthesis pathways are highly active in cancer cells and they utilise glycolytic by-products to produce energy and nucleotides for growth. Hence, the study further investigated the efficacy of two novel drugs that inhibit these pathways, namely NCT-503 and Physcion. The study is the first to show that the combination treatment of NCT-503 and Physcion substantially inhibited hepatocellular carcinoma growth in vitro and in vivo. The combination of fructose diet and metabolism-inhibiting drugs may provide a unique metabolic environment that warrants further investigation in targeting hepatocellular carcinoma.

Item ID: 64434
Item Type: Article (Research - C1)
ISSN: 2045-2322
Copyright Information: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
Funders: Robert W Storr Bequest to the Sydney Medical Foundation University of Sydney, National Health and Medical Research Council (NHMRC), Cancer Council New South Wales and Queensland (CC), James Cook University
Projects and Grants: NHMRC Project Grant APP1053206, Cancer Council NSW Project Grant 1069733, Cancer Council Qld Project Grant 1123436
Date Deposited: 29 Sep 2020 01:14
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111209 Solid Tumours @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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