Regulation of cell cycle by Pien Tze Huang in preventing hepatocellular carcinoma progression.

[BACKGROUND] Liver cancer remains a global health challenge, and it is estimated that by 2025, >1 million people will develop liver cancer annually. Chronic inflammation has a main causative relationship with liver cancer development by contributing to liver tumor initiation and progression. Growing clinical evidence suggests that Pien Tze Huang (PZH), a traditional Chinese medicine formula, may effectively inhibit the development of liver cancer. However, the mechanisms by which PZH intervenes in the multi-step hepatocarcinogenesis remain unexplored.

[PURPOSE] This study aimed to explore the effective components of PZH and advance pharmacological research on the treatment of liver cancer and multi-step hepatocarcinogenesis.

[METHODS] The chemical profiling of PZH was performed using UPLC-MS analysis, followed by identification of the target profiles for each compound through a network-based approach. Differential expression analysis was conducted using public transcriptomic datasets to identify molecular changes during the multi-step hepatocarcinogenesis. The effects of PZH on various biological functional modules were assessed through network target analysis and in vitro experiments.

[RESULTS] We found that PZH exerted its regulatory effects on the multi-step hepatocarcinogenesis through six key modules primarily involving cell cycle mediated pathways and biological processes. Cellular experiment revealed that PZH can inhibit cell proliferation, promote cell apoptosis, and regulate cell cycle-related pathways and biological processes by modulating the expression of molecules such as IL1B, IRAK1, and CREBBP.

[CONCLUSION] This study, integrating computational analysis, including network target and bioinformatics, with cellular experimental validation, reveals the inhibitory potential of PZH on hepatocellular carcinoma progression through the regulation of cell cycle-related pathways and biological processes. Notably, this study provides the first mechanistic insight into how PZH intervenes in the multi-step hepatocarcinogenesis, highlighting its potential role in preventing liver cancer development.