ArticleCurrent issues in molecular biology2026
Targeted Degradation of MCL-1 by PROTAC Mcl-1 Degrader-1 Exhibits Antiproliferative and Antimigratory Effects and Triggers Mitochondria-Mediated Apoptosis in Colorectal Cancer.
Article in Current issues in molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Myeloid cell leukemia-1 (MCL-1) is a cellular survival protein belonging to the Bcl-2 protein family and is overexpressed in human colorectal cancer (CRC).
backgroundThis study aimed to reduce cancer progression by suppressing the MCL-1 protein using PROTAC MCL-1 Degrader-1 and Trametinib, with the aim of overcoming the apoptosis resistance caused by high MCL-1 expression levels in colorectal cancer cells.
methodsTherefore, we tested the cell viability, proliferation, mitochondrial membrane potential, cell cycle progression, and cell death potential of MCL1-specific PROTAC Mcl-1 Degrader-1 and the combination of PROTAC Mcl-1 Degrader-1 and Trametinib in colorectal cancer cell lines using different methods such as WST-8 assays, real-time cell analysis, MMP/JC-1 staining assays, flow cytometry, and Western blot analysis.
resultsThe results suggest that PROTAC Mcl-1 Degrader-1 is associated with dose- and time-dependent reductions in cell proliferation in colorectal cancer cells. Under the experimental conditions used in this study, PROTAC MCL-1 Degrader-1 showed limited effects on the migratory potential of colorectal cancer cells but was associated with changes in cell cycle distribution, including an increased proportion of HT-29 cells in the G2/M phase. In addition, combination treatment with PROTAC MCL-1 Degrader-1 and trametinib was associated with greater reductions in cell viability and proliferation than either monotherapy. The combination treatment was also accompanied by changes in mitochondrial membrane potential and increased apoptotic cell populations, with a higher proportion of early apoptotic cells observed in HT-29 and COLO-205 colorectal cancer cell lines.
conclusionOur findings suggest that the reduction in MCL-1 protein levels observed following PROTAC Mcl-1 Degrader-1 treatment may contribute to its potential therapeutic relevance in colorectal cancer.
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