Bromodomain-containing protein 4 inhibitor JQ1 promotes melanoma cell apoptosis by regulating mitochondrial dynamics

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Bromodomain-containing protein 4 (BRD4) is implicated in various cancers, but its role in cutaneous melanoma requires further elucidation.
• Understanding BRD4's function in melanoma is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the effects of the BRD4 inhibitor JQ1 on B16 melanoma cells.
• To elucidate the mechanisms by which JQ1 affects mitochondrial dynamics, function, and apoptosis in melanoma.

Main Methods:

• Treatment of B16 melanoma cells with varying concentrations of JQ1 (125 nmol/L and 250 nmol/L).
• Analysis of mitochondrial respiratory chain complex subunits, reactive oxygen species (ROS) levels, and energy metabolism.
• Assessment of apoptosis, mitochondrial apoptosis pathway activation, and AMP-activated protein kinase (AMPK) activity.
• Evaluation of mRNA and protein levels of key mitochondrial dynamics proteins (Drp1, Mfn1, OPA1) and c-Myc.

Main Results:

• JQ1 treatment significantly downregulated mitochondrial respiratory chain complex subunits (I, III, IV, V) and increased ROS production.
• JQ1 induced energy metabolism dysfunction, enhanced apoptosis, and activated the mitochondrial apoptosis pathway.
• JQ1 inhibited AMPK activation and altered mitochondrial dynamics by increasing Drp1 and decreasing Mfn1 and OPA1.
• JQ1 reduced c-Myc expression, linking it to the observed changes in mitochondrial function and apoptosis.

Conclusions:

• BRD4 inhibition by JQ1 promotes melanoma cell apoptosis through mitochondrial dysfunction and altered dynamics.
• JQ1 impacts melanoma cell metabolism and survival by affecting the mitochondrial respiratory chain, ROS levels, and AMPK signaling.
• The findings highlight BRD4 as a potential therapeutic target in cutaneous melanoma, with JQ1 demonstrating anti-melanoma activity via mitochondrial pathways.