Decursin Suppresses Esophageal Squamous Cell Carcinoma Progression via Orchestrated Cell Cycle Deceleration,...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with few treatment options.
• There is a need for novel therapeutic strategies targeting ESCC.
• Decursin, a pyranocoumarin derivative, is being explored for its anticancer potential.

Purpose of the Study:

• To evaluate the antitumor efficacy of decursin against ESCC.
• To elucidate the underlying mechanisms of decursin's action in ESCC.
• To assess decursin's safety and therapeutic potential in preclinical models.

Main Methods:

• In vitro studies using ESCC cell lines (TE-1, KYSE-30, KYSE-150) and normal esophageal cells (Het-1A).
• Assays included cell viability, colony formation, wound healing, and Transwell migration/invasion.
• In vivo studies using subcutaneous xenograft models in mice.
• Mechanistic studies involved cell cycle analysis, apoptosis assays, and proteasome inhibition experiments.

Main Results:

• Decursin selectively inhibited ESCC cell viability (IC50: 14.62–26.20 μM) without harming normal cells.
• Decursin suppressed ESCC cell proliferation, migration, and invasion in vitro.
• Decursin significantly inhibited tumor growth in vivo with no observed systemic toxicity.
• Mechanistically, decursin induced G0/G1 cell cycle arrest and apoptosis via proteasomal degradation of TP63 and SOX2.

Conclusions:

• Decursin demonstrates significant antitumor activity against ESCC.
• Decursin's mechanism involves the proteasome-mediated degradation of oncoproteins TP63 and SOX2.
• Decursin is a promising therapeutic candidate for ESCC, warranting further clinical development.