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Published on: March 29, 2024
Molecular and functional anticancer effects of GLP/G9a inhibition by UNC0646 in MeWo melanoma cells
Luma Dayane de Carvalho Filiú-Braga1, Amanda Évelin Silva-Carvalho1, Marielly Reis Resende Sousa1
1Laboratório de Hematologia e Células-Tronco, Faculdade de Ciências da Saúde, Universidade de Brasília, Brasília-DF, Brazil.
Abstract:
In recent years, histone methyltransferases (HMTs) have emerged as important therapeutic targets in cancer due to their oncogenic role. Herein, we used the GLP/G9a inhibitor UNC0646 to assess whether the inhibition of such HMTs could induce cell death in MeWo melanoma cells. Furthermore, we investigated the cellular and molecular mechanisms involved in the observed cell death events. Finally, we performed a functional genomics analysis of 480 melanoma samples to characterize G9a/GLP involvement in melanoma. Interestingly, after UNC0646 treatment, MeWo cells underwent apoptosis, followed by loss of mitochondrial membrane potential and the generation of reactive oxygen species (ROS). Furthermore, MeWo cells treated with UNC0646 showed cell cycle arrest and inhibition of proliferation. At the molecular level, UNC0646 treatment increased the transcriptional levels of CDK1 and BAX, and decreased BCL-2 mRNA levels. Finally, we performed a functional enrichment analysis, which demonstrated that dozens of biological pathways were enriched in melanoma samples according to GLP and G9a expression, including apoptosis and necrosis. Taken together, our data show that inhibition of GLP/G9a using UNC0646 exerts anticancer effects on melanoma cells by controlling their proliferation and inducing apoptosis.
Insights
The histone methyltransferase inhibitor UNC0646 induces apoptosis and cell cycle arrest in melanoma cells. This study highlights GLP/G9a inhibition as a potential anticancer strategy for melanoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Histone methyltransferases (HMTs), including GLP/G9a, play oncogenic roles and are emerging therapeutic targets in cancer.
- Melanoma is a significant form of skin cancer where understanding novel therapeutic targets is crucial.
Purpose of the Study:
- To investigate the efficacy of the GLP/G9a inhibitor UNC0646 in inducing cell death in MeWo melanoma cells.
- To elucidate the cellular and molecular mechanisms underlying UNC0646-induced cell death.
- To analyze the involvement of G9a/GLP in melanoma through functional genomics.
Main Methods:
- Treatment of MeWo melanoma cells with the GLP/G9a inhibitor UNC0646.
- Assessment of apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS) generation, cell cycle, and proliferation.
- Analysis of gene expression changes (CDK1, BAX, BCL-2).
- Functional genomics analysis of 480 melanoma samples.
Main Results:
- UNC0646 treatment induced apoptosis, loss of mitochondrial membrane potential, and ROS generation in MeWo cells.
- Cell cycle arrest and inhibited proliferation were observed following UNC0646 treatment.
- Transcriptional analysis revealed increased CDK1 and BAX, and decreased BCL-2 mRNA levels.
- Functional enrichment analysis indicated GLP and G9a expression correlates with apoptosis and necrosis pathways in melanoma.
Conclusions:
- Inhibition of GLP/G9a by UNC0646 demonstrates anticancer effects against melanoma cells.
- UNC0646 controls melanoma cell proliferation and induces apoptosis, suggesting its potential as a therapeutic agent.
