Related Experiment Video
Updated: Apr 27, 2026
Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
Published on: April 15, 2016
Therapeutic effects of artesunate in hepatocellular carcinoma: repurposing an ancient antimalarial agent
Yves-Paul Vandewynckel1, Debby Laukens, Anja Geerts
1aDepartment of Hepatology and Gastroenterology bInfinity Imaging Lab, Medisip, iMinds cDepartment of Respiratory Medicine dGROUP-ID Consortium, Ghent University eDepartment of Pathology, Ghent University Hospital fUnit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium.
Objectives:
Artemisinins are antimalarial drugs that exert potent anticancer activity. We evaluated the effects of artesunate, a semisynthetic derivative of artemisinin, on tumor growth, angiogenesis, the unfolded protein response, and chemoresistance in hepatocellular carcinoma.
Materials And Methods:
The effect of artesunate was examined in HepG2 and BWTG3 cells under normoxic and hypoxic conditions and in a diethylnitrosamine-induced mouse model. Histology was performed with hematoxylin/eosin and reticulin staining. The expression of chemoresistance-related transporters and angiogenic and unfolded protein response factors was determined. Cytotoxicity was assessed by alanine and aspartate transaminase, lactate dehydrogenase, water-soluble tetrazolium salt, and caspase-3 activity assays. Small animal imaging was performed using dynamic contrast-enhanced MRI and choline PET to assess tumor progression.
Results:
Artesunate dose dependently reduced cell viability (from 50 μmol/l; P<0.05) and increased caspase-3 activity (P<0.05) in HepG2 and BWTG3 cells. These effects were enhanced by hypoxia (from 12.5 μmol/l; P<0.01). Moreover, artesunate downregulated vascular endothelial growth factor and placental growth factor expression in vitro (both P<0.05) and in vivo (both P<0.01). In mice, artesunate decreased vessel density and tumor burden (both P<0.05). These in-vivo effects were enhanced by combination with sorafenib (P<0.05 and P=0.07, respectively), without apparent hepatotoxicity. Furthermore, artesunate modulated the unfolded protein response in vitro and in vivo, increasing proapoptotic signaling, and did not induce doxorubicin chemoresistance.
Conclusion:
These findings indicate that artesunate could offer a new approach to the therapy of hepatocellular carcinoma. Clinical trials with artesunate as monotherapy or in combination with current hypoxia-inducing approaches are necessary.
Insights
Artesunate, an antimalarial drug, effectively reduces hepatocellular carcinoma cell viability and tumor growth by inhibiting angiogenesis and modulating the unfolded protein response. Further clinical trials are recommended for this promising cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited effective therapies.
- Artemisinins, known for their antimalarial properties, have demonstrated potential anticancer activities.
- Understanding the mechanisms of action of artesunate in HCC is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of artesunate in inhibiting tumor growth, angiogenesis, and the unfolded protein response (UPR) in hepatocellular carcinoma.
- To assess the impact of artesunate on chemoresistance in HCC models.
- To investigate the therapeutic potential of artesunate as a monotherapy or in combination with other agents for HCC treatment.
Main Methods:
- In vitro studies using HepG2 and BWTG3 cells under normoxic and hypoxic conditions.
- In vivo evaluation in a diethylnitrosamine-induced mouse model of HCC.
- Assessment of cytotoxicity, angiogenesis markers (VEGF, PlGF), UPR factors, and chemoresistance-related transporters.
- Histological analysis and small animal imaging (dynamic contrast-enhanced MRI, choline PET).
Main Results:
- Artesunate dose-dependently reduced HCC cell viability and increased apoptosis, with enhanced effects under hypoxia.
- Artesunate downregulated key angiogenic factors (VEGF, PlGF) and decreased tumor vessel density and burden in vivo.
- The drug modulated the UPR, promoting proapoptotic signaling without inducing doxorubicin chemoresistance.
- Combination therapy with sorafenib showed enhanced in vivo effects without significant hepatotoxicity.
Conclusions:
- Artesunate demonstrates significant anticancer effects in hepatocellular carcinoma by targeting tumor growth, angiogenesis, and UPR.
- Artesunate presents a promising new therapeutic approach for HCC, potentially as a monotherapy or in combination strategies.
- Further clinical investigation is warranted to establish the role of artesunate in HCC treatment, particularly with hypoxia-inducing therapies.
More Related Videos
09:11Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
Published on: May 24, 2024
06:38An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Related Concept Videos
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment