Triptolide Reduces Neoplastic Progression in Hepatocellular Carcinoma by Downregulating the Lipid Lipase Signaling Pathway

TL;DR

Triptolide fights liver cancer by reducing lipid buildup and inhibiting a key enzyme called lipoprotein lipase.

Contribution

This study reveals a new mechanism of triptolide in HCC treatment by targeting lipid metabolism and suppressing LPL activity.

Findings

Triptolide reduces lipid accumulation in hepatocellular carcinoma cells both in vitro and in vivo.

Lipoprotein lipase (LPL) is upregulated in HCC and its activity is directly suppressed by triptolide.

Triptolide inhibits HCC progression by transcriptionally suppressing LPL.

Abstract

TP is a widely utilized anticancer medication, particularly effective in treating HCC. Thorough investigation into TP’s molecular mechanism in HCC treatment is crucial for precise and combination therapy. In this paper, we have unveiled a novel mechanism of TP in HCC treatment, where it inhibits tumor growth by reducing lipid accumulation. While the inhibition of P53 gene activity is commonly thought to be the reason for TP’s effectiveness in treating HCC, this new mechanism serves as a significant complement to the current understanding, paving the way for innovative approaches to HCC treatment.

Hepatocellular carcinoma (HCC), which is the third leading cause of cancer-related mortality in the world, presents a significant medical challenge. Triptolide (TP) has been identified as an effective therapeutic drug for HCC. However, its precise therapeutic mechanism is still unknown. Understanding the mechanism of action of TP against HCC is crucial for its implementation in the field of HCC treatment. We hypothesize that the anti-HCC actions of TP might be related to its modulation of HCC lipid metabolism given the crucial role that lipid metabolism plays in promoting the progression of HCC. In this work, we first demonstrate that, both in vitro and in vivo, TP significantly reduces lipid accumulation in HCC cells. Additionally, we notice that lipoprotein lipase (LPL) expression is markedly upregulated in HCC, and that its levels are positively connected with the disease’s progression. It is interesting to note that TP dramatically reduces LPL activity, which in turn prevents HCC growth and reduces lipid accumulation. Additionally, the effect of TP on LPL is a direct correlation. These results definitely demonstrate that TP protects hepatocytes against abnormal accumulation of lipids by transcriptionally suppressing LPL, which reduces the development of HCC. This newly identified pathway provides insight into the process through which TP exerts its anti-HCC actions.

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