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Updated: Jun 10, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Parthenolide Inhibits Tumor Cell Growth and Metastasis in Melanoma A2058 Cells
Zahra Dorostgou1, Malihesadat Hosseiny2, Afsaneh Bahrami3
1Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran.
Background:
Skin melanoma is a potentially lethal cancer and ranks as the 17th most common cancer worldwide. Overcoming resistance to advanced-stage melanoma is a significant challenge in its treatment. Parthenolide (PAR) is recognized as a potent anticancer small molecule, yet its potential in treating melanoma is poorly investigated.
Objective:
Our objective was to investigate the apoptotic and anti-metastatic properties of PAR against the A2058 melanoma cells in vitro.
Methods:
This study employed various assays, such as cytotoxicity, apoptosis, cell cycle analysis, reactive oxygen species (ROS) production, mRNA expressions, western blotting, gelatin zymography, and scratch assay. The synergy between PAR and dacarbazine, a chemotherapy drug for treating skin cancer, was also assessed.
Results:
Our study revealed that PAR significantly reduced the viability of A2058 cancer cells, demonstrating greater potency against cancer cells compared to normal L929 cells (IC50: 20 μM vs. 27 μM after 24 h). PAR increased ROS production, elevated mRNA expression of pro-apoptotic Bax and NME1 genes, and decreased expression of the MITF gene. PAR induced apoptosis and cell cycle arrest in A2058 cells, as evidenced by the increased proportion of cells in the late apoptotic phase and sub-G1 cell cycle arrest. MMP-2 and MMP-9 mRNA and protein expressions, gelatinase activity, and the migration of A2058 cells were also decreased by PAR, suggesting its potential to suppress cancer cell invasion.
Conclusion:
These results, along with the synergic effect with dacarbazine, indicated that PAR may have the potential to be a therapeutic drug for melanoma by triggering apoptosis and suppressing invasion and migration.
Insights
Parthenolide (PAR) shows promise as a melanoma treatment by inducing cancer cell death and inhibiting metastasis. This study found PAR effectively reduced melanoma cell viability and invasion, with synergistic effects when combined with dacarbazine.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Skin melanoma is a significant global health concern, with advanced stages presenting treatment resistance challenges.
- Parthenolide (PAR), a potent small molecule, has shown anticancer properties but its efficacy in melanoma is under-explored.
Purpose of the Study:
- To investigate the apoptotic and anti-metastatic effects of Parthenolide (PAR) on A2058 melanoma cells in vitro.
- To assess the synergistic potential of PAR in combination with dacarbazine for melanoma treatment.
Main Methods:
- Cytotoxicity, apoptosis, cell cycle, reactive oxygen species (ROS) production, and gene expression (mRNA and protein) assays were performed.
- Western blotting, gelatin zymography, and scratch assays were utilized to evaluate invasion and migration.
- Synergy between PAR and dacarbazine was assessed.
Main Results:
- PAR significantly reduced A2058 melanoma cell viability (IC50: 20 μM) compared to normal cells (IC50: 27 μM).
- PAR induced apoptosis and cell cycle arrest, increased ROS production, and modulated pro-apoptotic (Bax, NME1) and anti-apoptotic (MITF) gene expression.
- PAR suppressed melanoma cell invasion and migration by decreasing MMP-2 and MMP-9 expression and activity.
Conclusions:
- Parthenolide (PAR) demonstrates significant potential as a therapeutic agent for melanoma by inducing apoptosis and inhibiting cancer cell invasion and migration.
- The observed synergistic effect of PAR with dacarbazine further supports its therapeutic potential in melanoma treatment.
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