Parthenolide induces ROS-dependent cell death in human gastric cancer cell
Dandan Han1, Wenhao Zhu2, Yang Chen1
1Department of Transfusion, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Background:
Parthenolide (PN), a key active ingredient of feverfew, has been used to treat gastrointestinal disorders. However, the mechanism of the cytotoxic effect exerted by PN on tumor cells has not been elucidated.
Objectives:
To study the cytotoxic effect of PN on human gastric cancer cells, the specific death mode, and gene expression changes induced by PN.
Material And Methods:
In this study, MGC-803 cells were used to study PN-induced cytotoxicity as a gastric cancer cell line. Assays of cell proliferation, cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed using a Cell Counting Kit-8 (CCK-8) assay and a flow cytometer. MGC-803 cells treated with and without PN were separately subjected to high-throughput RNA sequencing. Western blotting was used to investigate the expression of some important proteins.
Results:
Parthenolide exposure elicited cell proliferation inhibition in a doseand time-dependent manner. Parthenolide induced cell cycle arrest at the G1 and S stages. Parthenolide-induced caspase-dependent apoptosis and necroptosis were caused by the activation of RIP, RIP3 and MLKL. MGC-803 cells showed a response to ROS and oxidative stress after PN treatment. Moreover, ROS and cytotoxicity induced by PN were significantly attenuated by a ROS scavenger catalase.
Conclusions:
Parthenolide-induced gastric cancer cell death is a complex ROS-dependent process different from ordinary apoptosis and necrosis, suggesting that PN is a potential treatment option for gastric cancer.
Insights
Parthenolide from feverfew induces gastric cancer cell death through a complex, reactive oxygen species-dependent process involving apoptosis and necroptosis. This suggests its potential as a novel gastric cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Parthenolide (PN), derived from feverfew, has traditional uses for gastrointestinal issues.
- The precise mechanism of PN's cytotoxic effects on tumor cells remains largely uncharacterized.
Purpose of the Study:
- To investigate the cytotoxic impact of Parthenolide on human gastric cancer cells.
- To elucidate the specific cell death pathways and gene expression alterations induced by PN.
Main Methods:
- Utilized MGC-803 human gastric cancer cells.
- Performed cell proliferation, cell cycle, apoptosis, and reactive oxygen species (ROS) assays.
- Conducted high-throughput RNA sequencing and Western blotting to analyze gene and protein expression changes.
Main Results:
- PN inhibited gastric cancer cell proliferation in a dose- and time-dependent manner.
- PN induced cell cycle arrest at G1 and S phases, and triggered caspase-dependent apoptosis and RIPK-mediated necroptosis.
- PN treatment led to increased ROS production, which was mitigated by catalase, indicating ROS dependency.
Conclusions:
- Parthenolide induces gastric cancer cell death via a novel ROS-dependent mechanism, distinct from typical apoptosis or necrosis.
- Parthenolide demonstrates potential as a therapeutic agent for gastric cancer treatment.
Related Concept Videos
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...