PLK1 inhibition by Shikonin attenuates oral cancer growth through β-catenin-mediated regulation of EMT and apoptosis.

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy characterized by poor prognosis, frequent recurrence, and limited effective therapeutic options. Shikonin (Shk), a bioactive naphthoquinone derivative isolated from the roots of Lithospermum erythrorhizon, has emerged as a potent anticancer compound; however, its precise molecular targets and mechanisms of action in OSCC remain incompletely defined. The present study aimed to elucidate the molecular mechanism underlying Shikonin's anticancer activity by identifying its potential targets involved in oral tumour progression. In silico screening revealed Polo-like kinase 1 (PLK1), a pivotal mitotic regulator frequently overexpressed in cancers, as a key molecular target of Shikonin. Subsequent experimental validation demonstrated that Shikonin markedly suppressed OSCC cell proliferation, induced apoptosis, and triggered cell cycle arrest. Mechanistic investigations further uncovered that Shikonin downregulated PLK1 expression and perturbed its downstream signalling by modulating the β-catenin/epithelial-mesenchymal transition (EMT) axis, thereby enhancing DNA damage, mitochondrial dysfunction, and apoptotic response. Notably, siRNA-mediated silencing of PLK1 reproduced these phenotypic effects, substantiating PLK1 as a critical functional mediator of Shikonin's antitumor action. Collectively, these findings provide compelling evidence that Shikonin exerts its anticancer efficacy in OSCC through targeted inhibition of PLK1 via regulation of the β-catenin/EMT signalling network, highlighting its potential as a promising therapeutic candidate for oral cancer management.