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Published on: April 15, 2016
Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells
1Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), University of Chinese Academy of Sciences, Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
Abstract:
Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs for the prevention and treatment of solid tumors. Therefore, it is of significance to explore the potential activities of adenanthin on solid tumor cells. Here, we demonstrate that Prx I protein is essential for the survival of hepatocellular carcinoma (HCC) cells, and adenanthin can kill these malignant liver cells in vitro and xenografts. We also show that the cell death-inducing activity of adenanthin on HCC cells is mediated by the increased reactive oxygen species (ROS) levels. Furthermore, the silencing of Prx I or Prx II significantly enhances the cytotoxic activity of adenanthin on HCC, whereas the ectopic expression of Prx I and Prx II but not their mutants of adenanthin-bound cysteines can rescue adenanthin-induced cytotoxicity in Prxs-silenced HCC cells. Taken together, our results propose that adenanthin targets Prx I/II to kill HCC cells and its therapeutic significance warrants to be further explored in HCC patients.
Insights
Adenanthin, a natural compound, effectively kills liver cancer cells by targeting peroxiredoxins (Prx) I and II. This mechanism involves increased reactive oxygen species, suggesting potential therapeutic applications for hepatocellular carcinoma.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Peroxiredoxins (Prx) I and II are implicated in solid tumor progression.
- Adenanthin, a diterpenoid, targets Prx I/II and induces leukemic cell differentiation.
- The therapeutic potential of adenanthin in solid tumors remains largely unexplored.
Purpose of the Study:
- To investigate the efficacy of adenanthin against hepatocellular carcinoma (HCC) cells.
- To elucidate the mechanism underlying adenanthin's cytotoxic activity in HCC.
- To assess the role of Prx I/II in adenanthin's anti-cancer effects.
Main Methods:
- In vitro and xenograft models of HCC were used.
- Adenanthin's effect on HCC cell survival and reactive oxygen species (ROS) levels was assessed.
- Gene silencing and ectopic expression of Prx I/II were employed to study mechanism.
Main Results:
- Adenanthin demonstrated significant cytotoxicity against HCC cells in vitro and in vivo.
- Adenanthin-induced cell death was mediated by elevated ROS levels.
- Silencing Prx I/II enhanced adenanthin's cytotoxicity, while Prx I/II expression rescued this effect.
Conclusions:
- Adenanthin targets Prx I/II to induce cell death in HCC cells.
- The mechanism involves ROS generation and is dependent on adenanthin-binding cysteines in Prx I/II.
- Adenanthin shows therapeutic promise for hepatocellular carcinoma treatment.
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