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

Mingyu Ji1, Mulan Li2, Zhihong Zhou1

  • 1Guangxi Key Laboratory of Special Biomedicine; School of Medicine, Guangxi University, No. 100 East Daxue Road, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region 530004, China.

The Journal of Pharmacy and Pharmacology
|December 3, 2025
PubMed
Abstract

Insights

The novel compound Y01 effectively inhibits hepatocellular carcinoma (HCC) cell growth and migration while inducing apoptosis. This anticancer activity is linked to the inhibition of the PI3K/AKT/mTOR signaling pathway.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited effective therapeutic options.
  • Novel therapeutic agents targeting cancer cell proliferation, migration, and survival are urgently needed for HCC treatment.

Purpose of the Study:

  • To investigate the anti-HCC activity of a novel rhein derivative, Y01.
  • To elucidate the molecular mechanisms underlying Y01's potential anticancer effects in HCC.
  • To evaluate Y01 as a potential candidate for HCC therapy.

Main Methods:

  • Cell viability, proliferation, and colony formation assays (CCK-8, EdU, clone formation) were used to assess Y01's impact on HCC cells.
  • Apoptosis was evaluated using flow cytometry and western blotting.
  • Cell migration was assessed via wound healing and transwell assays, with mechanistic insights from transcriptomics and western blotting.

Main Results:

  • Y01 significantly suppressed HCC cell growth, colony formation, and migration.
  • Y01 treatment induced apoptosis in HCC cells and altered apoptosis-related protein expression.
  • Transcriptomic and western blotting analyses indicated that Y01 inhibits the PI3K/AKT/mTOR signaling pathway.

Conclusions:

  • Y01 demonstrates potent anti-HCC activity by inhibiting cell proliferation and migration.
  • Y01 induces apoptosis in HCC cells, potentially through the blockade of the PI3K/AKT/mTOR signaling pathway.
  • Y01 represents a promising therapeutic candidate for hepatocellular carcinoma.
Keywords:
PI3K/AKT/mTORapoptosishepatocellular carcinomarhein derivative

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