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Updated: Aug 2, 2025

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
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The endocannabinoid system, a new gatekeeper in the pharmacology of human hepatocellular carcinoma

Nasim Ebrahimi1, Nazanin Pazhouhesh Far2, Siavash Seifollahy Fakhr3

  • 1Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Iran.

Environmental Research
|April 16, 2023
PubMed

Insights

The endocannabinoid system shows potential for treating hepatocellular carcinoma (HCC), impacting cancer processes like apoptosis and cell invasion. Further research is needed to clarify its dual role in cancer development and treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) remains a leading cause of cancer death despite existing treatments.
  • The endocannabinoid system (ECS) has demonstrated anti-inflammatory and antitumor properties in various cancers.
  • Cannabinoid therapy is emerging as a potential treatment strategy for cancers, including HCC.

Purpose of the Study:

  • To review the multifaceted role of the endocannabinoid system in hepatocellular carcinoma.
  • To explore the potential of cannabinoids as a therapeutic approach for HCC.
  • To highlight the controversies and suggest future research directions regarding ECS in HCC.

Main Methods:

  • Literature review of preclinical and clinical studies on the endocannabinoid system and HCC.
  • Examination of ECS involvement in cancer-related pathways such as ER stress, apoptosis, autophagy, and EMT.
  • Analysis of the relationship between ECS, microRNAs, and metabolic reprogramming in HCC.

Main Results:

  • The ECS influences key cancer processes including apoptosis, autophagy, cell invasion, EMT, and cancer stem cell phenotypes in HCC.
  • Alterations in ECS signaling may serve as diagnostic and prognostic biomarkers for HCC.
  • The ECS impacts metabolic reprogramming and exosome lipid content, relevant to HCC progression.

Conclusions:

  • The endocannabinoid system plays a complex role in HCC, with evidence supporting both carcinogenic and anticancer effects.
  • Further detailed molecular and preclinical studies are crucial to elucidate the therapeutic or carcinogenic impacts of endocannabinoids in HCC.
  • Understanding the heterogeneity of HCC is essential for developing effective cannabinoid-based therapies.
Keywords:
ApoptosisCancer stem cellsEndocannabinoidsEndoplasmic reticulum (ER) stressNanoparticlesNovel cancer therapyTumorigenesis

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