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Anti-Proliferative and Anti-Migratory Activities of Hispidulin on Human Melanoma A2058 Cells
Chi-Jen Chang1,2, Yen-Ling Hung3, Ting-Chen Chen3
1School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
Abstract:
Melanoma represents less than 5% of skin cancers, but is the most lethal, mainly because of its high-metastatic potential and resistance to various therapies. Therefore, it is important to develop effective treatments, especially chemotherapeutic drugs with cytotoxicity, anti-metastaticity, and few side effects. One such natural product is hispidulin, a flavone distributed in plants of the Asteraceae. Previous studies have demonstrated that hispidulin has various pharmacological benefits, such as anti-tumor, anti-inflammation, and anti-allergic effects. This study aims to explore the effects of hispidulin against melanoma in vitro and in vivo. Results revealed that hispidulin selectively decreased the cell viability of A2058 cells in a dose- and time-dependent manner. Hispidulin induced cells accumulated in the sub-G1 phase via activating caspase 8 and 9, increased cleaved caspase 3, and cleaved PARP expression. Hispidulin was able to decrease AKT and ERK phosphorylation, which facilitated cell growth and survival. Moreover, hispidulin promoted reactive oxygen species generation in cells and suppressed cell migration through downregulated matrix metalloproteinase-2 expression. Hispidulin significantly inhibited tumor growth in a xenograft model. Based on these results, hispidulin produces its anti-melanoma effects by inducing cancer cell apoptosis and reducing its migration. Therefore, we suggest hispidulin as a potent therapeutic candidate for melanoma treatment.
Insights
Hispidulin, a natural flavone, effectively combats melanoma by inducing cancer cell apoptosis and reducing metastasis. This study suggests hispidulin as a promising therapeutic candidate for melanoma treatment.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Melanoma is a lethal skin cancer with high metastatic potential and therapeutic resistance.
- There is a need for effective melanoma treatments with cytotoxicity and anti-metastatic properties.
- Hispidulin, a natural flavone, exhibits known anti-tumor and anti-inflammatory effects.
Purpose of the Study:
- To investigate the anti-melanoma effects of hispidulin in vitro and in vivo.
- To explore the mechanisms underlying hispidulin's anti-melanoma activity.
- To evaluate hispidulin as a potential therapeutic agent for melanoma.
Main Methods:
- Assessed hispidulin's effect on A2058 melanoma cell viability and apoptosis.
- Analyzed cell cycle progression, caspase activation, and signaling pathways (AKT, ERK).
- Evaluated reactive oxygen species generation, matrix metalloproteinase-2 (MMP-2) expression, and tumor growth in a xenograft model.
Main Results:
- Hispidulin reduced melanoma cell viability and induced apoptosis via caspase activation (caspase 8, 9, 3) and PARP cleavage.
- Hispidulin inhibited cell growth and survival pathways by decreasing AKT and ERK phosphorylation.
- Hispidulin suppressed cell migration by downregulating MMP-2 and inhibited tumor growth in vivo.
Conclusions:
- Hispidulin demonstrates potent anti-melanoma effects through apoptosis induction and migration suppression.
- Hispidulin selectively targets melanoma cells and inhibits tumor progression.
- Hispidulin is a promising natural therapeutic candidate for melanoma treatment.
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