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KMID : 0032220230350030217
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Annals of Dermatology
2023 Volume.35 No. 3 p.217 ~ p.228
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Curcumin Enhances the Anticancer Effects of Binimetinib on Melanoma Cells by Inducing Mitochondrial Dysfunction and Cell Apoptosis with Necroptosis
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Lee Yoon-Jin
Heo Jae-Young
Kim Dong-Sung
Choi Yu-Sung
Kim Soo-Young
Nam Hae-Seon
Lee Sang-Han
Cho Moon-Kyun
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Abstract
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Background: Recent studies suggest that MEK1/2 inhibitors, including binimetinib, signifi- cantly 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 bin- imetinib 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, mi- gration, death, and reactive oxygen species (ROS) production following single therapy treat- ment, 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 bin- imetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.
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KEYWORD
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Apoptosis, Binimetinib, Curcumin, Melanoma, Necroptosis, Reactive oxygen species
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