Related Experiment Video

Updated: Nov 22, 2025

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

168

HTBPI, an active phenanthroindolizidine alkaloid, inhibits liver tumorigenesis by targeting Akt

Hongwei Liu1, Qian Chen1, Di Lu2

  • 1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 7, 2021
PubMed

Insights

A novel compound, HTBPI, effectively inhibits hepatocellular carcinoma (HCC) cell growth by targeting Akt. This Akt inhibitor promotes apoptosis and autophagy, offering a potential new therapy for liver cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Akt signaling is vital for hepatocellular carcinoma (HCC) cell survival and represents a therapeutic target.
  • Developing novel Akt inhibitors is crucial for effective HCC treatment strategies.

Purpose of the Study:

  • To investigate the potential of the phenanthroindolizidine alkaloid HTBPI as an Akt inhibitor for HCC therapy.
  • To elucidate the mechanisms by which HTBPI suppresses HCC cell proliferation.

Main Methods:

  • In vitro and in vivo studies using HCC cell lines and animal models.
  • Assays including CETSA and DARTS to confirm target engagement.
  • Analysis of apoptosis and autophagy markers.
  • Overexpression studies to validate Akt's role.

Main Results:

  • HTBPI significantly suppressed HCC cell proliferation by inducing apoptosis and autophagy.
  • HTBPI directly targeted Akt at the Thr 308 kinase binding domain, inhibiting its activity.
  • Combined treatment with HTBPI and bafilomycin A1 enhanced apoptosis.
  • Ectopic Akt overexpression counteracted HTBPI's inhibitory effects.
  • High p-Akt (Thr 308) levels correlated with poor prognosis in HCC patients.

Conclusions:

  • HTBPI is a promising Akt inhibitor that impedes HCC progression by modulating apoptosis and autophagy.
  • HTBPI's interaction with p-Akt (Thr 308) offers a potential therapeutic strategy for HCC patients.
Keywords:
HTBPIan active phenanthroindolizidine alkaloidliver tumorigenesisp‐Akt (Thr 308)

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