Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, often driven by abnormal lipid metabolism and excessive blood vessel growth.
In a new study, researchers from Fudan University and Wenzhou Medical University have uncovered how disulfiram—a long-used anti-alcoholism medication—exerts potent anti-tumour effects in liver cancer.
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The team found that disulfiram acts as a copper ionophore to downregulate an RNA methylase called TRMT10C.
This reduction in TRMT10C activity decreases methylation on the mRNA of c-FOS, a transcription factor, leading to its increased expression.
Elevated c-FOS then suppresses two critical downstream targets: PCSK9 (involved in lipid metabolism) and CD146 (a promoter of angiogenesis).
Experiments in cell lines and mouse models showed that disulfiram alone—or in combination with the anti-angiogenic drug thalidomide—significantly inhibited tumour growth, reduced lipid droplet accumulation, and blocked new blood vessel formation.
Clinical data from HCC patients further supported the relevance of this pathway: high TRMT10C and PCSK9 expression correlated with poor prognosis, while high c-FOS was associated with better survival.
“Our findings reveal a previously unknown mechanism by which disulfiram combats liver cancer through RNA epigenetic regulation,” said corresponding author Jinglin Xia.
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“This not only provides a new therapeutic strategy but also supports drug repurposing as a viable approach in oncology.”
The study was published in Science China Life Sciences.
Source: Science China Press
