Ginsenoside Rg3 suppresses FUT4 expression through inhibiting NF-κB/p65 signaling pathway to promote melanoma cell...

Area of Science:

• Cancer Biology
• Molecular Oncology
• Pharmacology

Background:

• Abnormal glycosylation, specifically increased fucosyltransferase IV (FUT4), is linked to cancer progression and apoptosis.
• Nuclear factor kappa B (NF-κB) signaling plays a critical role in regulating cell growth and apoptosis.
• Ginsenoside Rg3, an herbal compound, exhibits potent antitumor properties.

Purpose of the Study:

• To investigate whether Ginsenoside Rg3's antitumor effects involve the modulation of NF-κB signaling and FUT4 expression.
• To elucidate the mechanisms by which Rg3 influences tumor cell apoptosis and growth.

Main Methods:

• Assessing the impact of Rg3 on NF-κB pathway components, including DNA binding and transcriptional activity.
• Evaluating FUT4 promoter activity and expression levels following Rg3 treatment.
• Utilizing NF-κB inhibitors and siRNA to confirm the role of NF-κB in FUT4 regulation.
• Examining apoptotic pathway activation (extrinsic and intrinsic) in response to Rg3.
• Testing Rg3 efficacy in a melanoma xenograft mouse model.

Main Results:

• Ginsenoside Rg3 suppressed FUT4 expression by inhibiting NF-κB binding to the FUT4 promoter.
• Rg3 reduced NF-κB signaling molecules, DNA binding activity, and transcriptional activity.
• Pharmacological inhibition or knockdown of NF-κB (p65) also decreased FUT4 expression.
• Rg3 treatment activated both extrinsic and intrinsic apoptotic pathways.
• In vivo, Rg3 downregulated FUT4 and NF-κB/p65, suppressed melanoma growth, and induced apoptosis without toxicity.

Conclusions:

• Ginsenoside Rg3 induces tumor cell apoptosis through the inhibition of NF-κB signaling pathway-mediated FUT4 expression.
• Rg3 demonstrates potential as a novel therapeutic agent for melanoma treatment.