2. Academic Validation
  3. A novel rhein derivative Y01 inhibits hepatocellular carcinoma by inducing apoptosis through regulating PI3K/AKT/mTOR pathway

A novel rhein derivative Y01 inhibits hepatocellular carcinoma by inducing apoptosis through regulating PI3K/AKT/mTOR pathway

  • J Pharm Pharmacol. 2025 Dec 3:rgaf120. doi: 10.1093/jpp/rgaf120.
Mingyu Ji 1,  Mulan Li 2,  Zhihong Zhou 1,  Limei Yang 1,  Dong Ran 3,  Tingting Yang 1,  Lele Yang 1,  Wei Tian 4,  Peilin Yang 1 5 6 7
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Special Biomedicine; School of Medicine, Guangxi University, No. 100 East Daxue Road, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region 530004, China.
  • 2 The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
  • 3 Department of Medicine Laboratory, The Eighth People's Hospital of Nanning, No. 63 West Mingxiu Road, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region 530003, China.
  • 4 Guangxi International Zhuang Medicine Hospital, No. 8 Qiuyue Road, Liangqing District, Nanning, Guangxi Zhuang Autonomous Region 530201, China.
  • 5 Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, State Key Laboratory of Targeting Oncology, Pharmaceutical College, Guangxi Medical University, No. 22 Shuangyong Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
  • 6 Key Laboratory of Basic Research on Regional Diseases of Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, No. 22 Shuangyong Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
  • 7 Key Laboratory of Prevention and Control of Highly Prevalent Diseases of Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, No. 22 Shuangyong Road, Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region 530021, China.
PMID: 41332198 DOI: 10.1093/jpp/rgaf120
Abstract

Purpose: The aim of this study was to evaluate the novel rhein derivative Y01 for its anti-HCC activity and potential molecular mechanisms, thereby positioning it as a promising candidate for HCC therapy.

Methods: CCK-8, EdU incorporation and clone formation assay were employed to assess the impact of Y01 on the cell viability and proliferation of HCC cells. While Apoptosis was assessed through flow cytometry and western blotting techniques. Additionally, the impact of Y01 on cell mobility was evaluated via wound healing and transwell migration assays, with western blotting analyses providing further insights. Mechanistically, transcriptomics and western blotting assays were used to explore the potential signaling pathways.

Results: Y01 markedly suppressed the growth, colony formation, and migratory capacity of HCC cells, induced Apoptosis and affected the expression of apoptosis-related proteins. Transcriptomics initially pointed toward the PI3K/Akt/mTOR pathway as a potential target, which was corroborated by western blotting results showing decreased levels of phosphorylated PI3K, Akt, and mTOR following Y01 treatment, highlighting its role in mediating the compound's Anticancer effects.

Conclusions: Y01 inhibited the proliferation, migration, and induced Apoptosis of HCC cells possibly by blocking PI3K/Akt/mTOR signaling pathway.

Keywords

PI3K/AKT/mTOR; apoptosis; hepatocellular carcinoma; rhein derivative.

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