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Updated: Mar 23, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Giganteaside D induces ROS-mediated apoptosis in human hepatocellular carcinoma cells through the MAPK pathway
Junshan Liu1, Xiduan Wei1, Yafeng Wu2
1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People's Republic of China.
Purpose:
Every year, almost one million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide and more than 690,000 patients die of it. At present, most therapeutic anti-HCC agents are not effective, which is due to the appearance of chemo-resistance and/or toxic side effects. Therefore, it is imperative to find novel more effective anti-HCC agents. Here, we evaluated the effect of giganteaside D (GD), an oleanolic acid saponin from P. scabiosaefolia, on the growth and apoptosis of HCC cells.
Methods And Results:
Using MTT and clonogenic assays, we found that GD exhibited a significant growth inhibitory effect on the HCC-derived cell lines HepG2 and Bel-7402. In addition, we found that GD induced mitochondria-mediated apoptosis in these HCC-derived cells, as indicated by a decreased mitochondrial potential, activation of Caspase-9 and Caspase-3, cleavage of PARP and release of Cytochrome C from the mitochondria. Besides, we found that GD stimulated the generation of reactive oxygen species (ROS) and that blockage of ROS attenuated the GD-induced mitochondria-mediated apoptosis. Additionally, we found that GD treatment led to a decrease in phosphorylated Erk (p-Erk) and triggered the generation of p-JNK, both components of the mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of Erk or JNK by specific inhibitors or siRNAs augmented or attenuated the cytotoxic and apoptotic effects of GD.
Conclusions:
From our results we conclude that GD can induce ROS-mediated apoptosis in HCC-derived cells through the MAPK pathway. This observation may open up avenues to explore the future use of GD as a HCC chemotherapeutic agent.
Insights
Giganteaside D (GD) effectively inhibits hepatocellular carcinoma (HCC) cell growth and induces apoptosis. This natural compound shows promise as a novel HCC chemotherapeutic agent by activating cell death pathways.
Area of Science:
- Pharmacology
- Cancer Biology
- Natural Products Chemistry
Background:
- Hepatocellular carcinoma (HCC) affects nearly one million individuals annually, with high mortality due to chemo-resistance and toxic side effects of current treatments.
- There is a critical need for novel, more effective anti-HCC agents to improve patient outcomes.
- Giganteaside D (GD), a saponin derived from P. scabiosaefolia, is investigated for its potential anti-cancer properties.
Purpose of the Study:
- To evaluate the efficacy of giganteaside D (GD) in inhibiting the growth of hepatocellular carcinoma (HCC) cells.
- To investigate the mechanisms underlying GD's effects on HCC cell apoptosis and survival.
Main Methods:
- MTT and clonogenic assays were employed to assess the growth inhibitory effects of GD on HCC cell lines (HepG2, Bel-7402).
- Mitochondrial-mediated apoptosis was analyzed by measuring mitochondrial potential, Caspase-9, Caspase-3 activation, PARP cleavage, and Cytochrome C release.
- Reactive oxygen species (ROS) generation and the mitogen-activated protein kinase (MAPK) pathway (Erk, JNK) were investigated.
Main Results:
- GD demonstrated significant growth inhibition in HepG2 and Bel-7402 HCC cell lines.
- GD induced mitochondria-mediated apoptosis, evidenced by decreased mitochondrial potential and activation of key apoptotic markers.
- GD treatment increased ROS generation and modulated MAPK signaling (decreased p-Erk, increased p-JNK), influencing apoptosis.
Conclusions:
- Giganteaside D (GD) effectively induces apoptosis in HCC-derived cells via ROS generation and the MAPK pathway.
- These findings suggest that GD holds potential as a novel chemotherapeutic agent for hepatocellular carcinoma.
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