5'-Methylthioadenosine and Cancer: old molecules, new understanding

Abstract

While the metabolic changes in cancer tissues were first observed by Warburg Otto almost a century ago, altered metabolism has recently returned as a focus of cancer research. 5'-Methylthioadenosine (MTA) is a naturally occurring sulfur-containing nucleoside found in numerous species. While MTA was first isolated several decades ago, a lack of sensitive and specific analytical methodologies designed for its direct quantification has hampered the study of its physiological and pathophysiological features. Many studies indicate that MTA suppresses tumors by inhibiting tumor cell proliferation, invasion, and the induction of apoptosis while controlling the inflammatory micro-environments of tumor tissue. In this review, we assessed the effects of MTA and of related materials on the growth and functions of normal and malignant cells.

Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells

“…In high methionine condition there was also an increase of two direct methionine derivatives, the regulatory metabolite methylthioadenosine (MTA) and the toxic compound methionine sulfoxide ( Figure 4 D). Remarkably, the MTA level negatively correlates with growth potential in the liver [ 36 , 37 ]. In fact, it has been reported that MTA decreases after partial hepatectomy, when the replicative response of hepatocytes is higher [ 38 ], and MTA administration in vitro reduces liver cell growth [ 39 ].…”

“…In fact, it has been reported that MTA decreases after partial hepatectomy, when the replicative response of hepatocytes is higher [ 38 ], and MTA administration in vitro reduces liver cell growth [ 39 ]. Furthermore, MTA inhibits the synthesis of polyamines [ 36 ], whose level is correlated with proliferation and which were indeed decreased in high methionine condition (see spermidine and putrescine, Figure 4 E). On the contrary, the MTA derivatives adenine and adenosine increased in high methionine condition ( Figure 4 E).…”

Loss of function in the Drosophila clock gene period results in altered intermediary lipid metabolism and increased susceptibility to starvation

“…Figure 5). Methylthioadenosine, a product of the polyamine metabolism that affects various metabolic and cellular processes including cell growth [43,44], was also lower in bodies of n per 01 relative to n WT CS (Suppl. Figure 6e).…”

Functional Metabolomics Analysis Elucidating the Metabolic Biomarker and Key Pathway Change Associated With the Chronic Glomerulonephritis and Revealing Action Mechanism of Rhein

“…The effects of MTA are accompanied by inhibition of circulating tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) expression, and stimulation of IL-10 synthesis. MTA can inhibit the transcriptional activation of iNOS by proinflammatory cytokines in liver cells, inhibit the induction of COX2 in raw264.7 cells, inhibit p38 mitogen-activated protein kinase (MAPK), c-jun phosphorylation, inhibitor kappa B alpha (IB) degradation, and nuclear factor B (NFĸB) activation, all of which are signaling pathways related to the production of inflammatory mediators ( Eloranta et al., 1982 ; Li Y. et al., 2019 ).…”