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Updated: Dec 28, 2025
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Metalloproteinases Suppression Driven by the Curcumin Analog DM-1 Modulates Invasion in BRAF-Resistant Melanomas
Nayane de Souza1, Érica Aparecida de Oliveira1, Fernanda Faião-Flores1
1Skin Biology Group, Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of Sao Paulo, FCF/USP, Brazil.
Background:
Melanoma is the most aggressive skin cancer, and BRAF (V600E) is the most frequent mutation that led to the development of BRAF inhibitors (BRAFi). However, patients treated with BRAFi usually present recidivism after 6-9 months. Curcumin is a turmeric substance, and it has been deeply investigated due to its anti-inflammatory and antitumoral effects. Still, the low bioavailability and biodisponibility encouraged the investigation of different analogs. DM-1 is a curcumin analog and has shown an antitumoral impact in previous studies.
Methods:
Evaluated DM-1 stability and cytotoxic effects for BRAFi-sensitive and resistant melanomas, as well as the role in the metalloproteinases modulation.
Results:
DM-1 showed growth inhibitory potential for melanoma cells, demonstrated by reduction of colony formation, migration and endothelial tube formation, and cell cycle arrest. Subtoxic doses were able to downregulate important Metalloproteinases (MMPs) related to invasiveness, such as MMP-1, -2 and -9. Negative modulations of TIMP-2 and MMP-14 reduced MMP-2 and -9 activity; however, the reverse effect is seen when increased TIMP-2 and MMP-14 resulted in raised MMP-2.
Conclusion:
These findings provide essential details into the functional role of DM-1 in melanomas, encouraging further studies in the development of combinatorial treatments for melanomas.
Insights
DM-1, a curcumin analog, inhibits melanoma cell growth and migration. It also modulates metalloproteinases, offering potential for new melanoma treatments when BRAF inhibitors fail.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Melanoma, a severe skin cancer, often involves the BRAF (V600E) mutation, targeted by BRAF inhibitors (BRAFi).
- BRAFi treatment leads to patient relapse within 6-9 months due to resistance.
- Curcumin analogs, like DM-1, are explored for antitumoral effects, addressing curcumin's bioavailability issues.
Purpose of the Study:
- To assess DM-1's efficacy against BRAFi-sensitive and resistant melanoma cells.
- To investigate DM-1's impact on metalloproteinase (MMP) activity and melanoma invasiveness.
Main Methods:
- Evaluating DM-1's stability and cytotoxic effects on melanoma cell lines.
- Assessing DM-1's influence on colony formation, migration, and cell cycle progression.
- Analyzing DM-1's modulation of MMPs (MMP-1, -2, -9) and their inhibitors (TIMP-2, MMP-14).
Main Results:
- DM-1 demonstrated significant growth inhibition, reduced colony formation, migration, and induced cell cycle arrest in melanoma cells.
- Subtoxic DM-1 doses downregulated key invasiveness-related MMPs (-1, -2, -9).
- DM-1 modulated TIMP-2 and MMP-14, affecting MMP-2 and -9 activity, with complex dose-dependent effects.
Conclusions:
- DM-1 exhibits potent anti-melanoma properties, including growth inhibition and modulation of invasion-related factors.
- Findings highlight DM-1's potential role in overcoming BRAFi resistance.
- Further research into DM-1 for combinatorial melanoma therapy is warranted.
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