Ann Dermatol.  2023 Jun;35(3):217-228. 10.5021/ad.22.200.

Curcumin Enhances the Anticancer Effects of Binimetinib on Melanoma Cells by Inducing Mitochondrial Dysfunction and Cell Apoptosis with Necroptosis

• Lee YJ
• Heo JY
• Kim DS
• Choi YS
• Kim S
• Nam HS
• Lee SH
• Cho MK

• KMID: 2542656
• DOI: http://doi.org/10.5021/ad.22.200

Abstract

Background
Recent studies suggest that MEK1/2 inhibitors, including binimetinib, significantly improve malignant melanoma (MM) patient survival. Growing evidence suggests that phytochemicals, especially curcumin, can overcome drug resistance in cancer cells through a variety of mechanisms.
Objective
This study aims to examine curcumin’s efficacy in vitro combined with binimetinib in human MM cells.
Methods
We used 2D monolayer and 3D spheroid human epidermal melanocyte culture models, HEMn-MP (human epidermal melanocytes, neonatal, moderately pigmented), and two human MM cell lines, G361 and SK-MEL-2, to evaluate cell viability, proliferation, migration, death, and reactive oxygen species (ROS) production following single therapy treatment, with either curcumin or binimetinib, or a combination of both.
Results
Compared to MM cells treated with single therapy, those with combination therapy showed significantly decreased cell viability and increased ROS production. We observed apoptosis following both single and combination therapies. However only those who had had combination therapy had necroptosis.
Conclusion
Collectively, our data demonstrates that curcumin exerts significant synergistic anticancer effects on MM cells by inducing ROS and necroptosis when combined with binimetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.

Keyword

Apoptosis; Binimetinib; Curcumin; Melanoma; Necroptosis; Reactive oxygen species