Nobiletin Inhibits Non-Small-Cell Lung Cancer by Inactivating WNT/β-Catenin Signaling through Downregulating...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Nobiletin exhibits anticancer properties, but its precise mechanism of action remains largely unknown.
• Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related mortality worldwide.

Purpose of the Study:

• To elucidate the anticancer mechanism of nobiletin in NSCLC.
• To investigate the role of nobiletin in regulating cancer stemness and signaling pathways in NSCLC cells.

Main Methods:

• Assessed nobiletin's effects on NSCLC cell proliferation, migration, and apoptosis using soft agar, Transwell, and apoptosis assays.
• Measured cancer stemness via sphere formation assays.
• Identified nobiletin-regulated genes and miRNAs using whole-genome sequencing, western blotting, and immunofluorescence.

Main Results:

• Nobiletin significantly inhibited NSCLC colony and sphere formation while inducing apoptosis.
• Nobiletin upregulated WNT/β-catenin signaling inhibitors (NKD1, AXIN2, WIF1) and downregulated β-catenin and its downstream targets (c-Myc, c-Jun, cyclin D1).
• Nobiletin suppressed miR-15-5p expression, with NKD1, AXIN2, and WIF1 identified as its targets.

Conclusions:

• Nobiletin demonstrates potent inhibitory effects against NSCLC.
• Nobiletin exerts its anticancer role by inhibiting the miR-15-5p/β-catenin signaling pathway in NSCLC.