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
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.