Decursin Suppresses Esophageal Squamous Cell Carcinoma Progression via Orchestrated Cell Cycle Deceleration, Apoptotic Activation, and Oncoprotein Degradation

TL;DR

Decursin, a natural compound, shows promise in treating esophageal cancer by stopping tumor growth and reducing harmful proteins.

Contribution

Decursin's novel mechanism involves proteasomal degradation of oncoproteins TP63 and SOX2 in ESCC.

Findings

Decursin selectively inhibits ESCC cell viability without harming normal cells.

Decursin reduces tumor growth in xenograft models without systemic toxicity.

Decursin induces cell cycle arrest and apoptosis via proteasome-mediated oncoprotein degradation.

Abstract

Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy with limited therapeutic options. This study investigated the antitumor efficacy and mechanisms of decursin, a natural pyranocoumarin derivative, against ESCC. In vitro analyses demonstrated that decursin selectively inhibited ESCC cell viability (IC50: 14.62 ± 0.61–26.20 ± 2.11 μM across TE-1, KYSE-30, and KYSE-150 cell lines) without affecting normal esophageal epithelial cells (Het-1A). Decursin (10 μM) suppressed colony formation, impaired wound healing (p < 0.001 at 48 h), and reduced Transwell migration/invasion in KYSE-150 cells. Subcutaneous xenograft models revealed significant tumor growth inhibition (p < 0.01) with decursin treatment (10 mg/kg, intraperitoneal), accompanied by no systemic toxicity. Mechanistically, decursin induced G0/G1 cell cycle deceleration (p < 0.01) and apoptosis through ubiquitin–proteasome-mediated degradation of oncoproteins TP63 and SOX2. Time- and dose-dependent protein suppression was reversed by proteasome inhibitor MG-132, but unaffected by lysosomal inhibition. These findings establish decursin as a promising therapeutic agent for ESCC, functioning via proteasomal degradation of key oncogenic drivers, and provide a rationale for decursin’s further development as a targeted monotherapy or chemosensitizer in multimodal regimens.

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