Costunolide suppresses oral squamous cell carcinoma cell progression through modulation of miR-655–3p expression

Oral squamous cell carcinoma (OSCC) accounts for 90 % of oral malignancies, with a poor 5-year survival rate (<50 %) and limited treatment options. This study investigated the anti-tumor effects of costunolide, a natural compound from Aucklandia, on OSCC, focusing on its regulation of miR-655–3p and downstream pathways. Tumor tissues from 40 OSCC patients and controls were collected. OSCC cells were treated with different dose of costunolide or transfected with miR-655–3p mimics or anti-miRs. Cell proliferation, migration, invasion, and expression of miR-655–3p, and E-cadherin and N-cadherin were evaluated by CCK-8, colony formation, wound healing assay, Transwell, qRT-PCR and Western blot assays. The expression level of miR-655–3p was significantly downregulated in both OSCC tumor tissues and cell lines (P < 0.05). Costunolide demonstrated a dose-dependent inhibitory effect on SCC-3 cell proliferation, with inhibition rates of 23.12 ± 2.33 %, 45.74 ± 4.63 %, and 61.11 ± 5.23 % at low, medium, and high doses, respectively (all P < 0.05 vs control group). Concurrently, it markedly reduced colony formation capacity (high-dose group: 38.38 ± 3.74 vs control: 86.96 ± 6.60, P < 0.05). Furthermore, Costunolide treatment significantly attenuated metastatic potential, decreasing cell migration rate (high-dose: 23.81 ± 2.15 % vs control: 69.85 ± 4.66 %) and invasive ability (56.27 ± 4.98 vs 116.83 ± 10.46 cells/field), while upregulating E-cadherin (0.57 ± 0.04 vs 0.17 ± 0.02) and downregulating N-cadherin expression (0.32 ± 0.03 vs 0.73 ± 0.06). Mechanistically, costunolide substantially enhanced miR-655–3p expression. Functional studies confirmed that miR-655–3p overexpression mimicked costunolide's effects by suppressing proliferation, migration and invasion, along with modulating EMT markers, whereas miR-655–3p knockdown effectively reversed costunolide's antitumor activity in OSCC cells. Costunolide inhibits proliferation, migration, invasion and EMT in OSCC cells via regulation of miR-655–3p expression. This study reveals a novel mechanism of costunolide and highlights miR-655–3p as a therapeutic target, offering a promising natural-derived strategy for OSCC treatment.