Available online 17 December 2025

Rosmarinic acid (RA), a phenolic compound demonstrating therapeutic effects including anticancer properties. Cisplatin, a chemotherapeutic agent, is widely employed in cancer treatment. Head and neck squamous cell carcinoma (HNSCC) exhibits high mortality rates, frequently resistance to cisplatin-based regimens. Cisplatin and RA combination enhanced cisplatin efficiency across various tumor types. This study aimed to elucidate the effects of cisplatin-RA combination on cell proliferation, apoptosis and migration in HNSCC cell lines.

Primary HNSCC cell lines (HN18/HN30) and metastatic HNSCC cell lines (HN17/HN31) were employed in this investigation. Cells underwent treatment with rosmarinic acid (100-1,000 μM) or cisplatin (5–40 μM) for 72 h, followed by cell viability assessment using MTT assay. The combinatorial cisplatin-RA treatment effects on cell proliferation inhibition were quantified using MTT assay, with calculation of the combination index to assess synergistic interactions. Synergistic effects of cisplatin-RA combination on apoptosis and cell migration were evaluated in HNSCC cell lines through flow cytometric analysis and scratch assay, respectively.

Both cisplatin and rosmarinic acid demonstrated concentration-dependent reductions in HNSCC cell viability. Combination index of cisplatin-RA interaction indicating synergistic interactions in HN17, HN30 and HN31 cells. Cisplatin (20 μM) with RA (400 μM) combination synergistically induced apoptosis in HN18 and HN17 cells, while cisplatin (20 μM) and RA (800 μM) combination demonstrated synergistic apoptotic induction in HN30 and HN31 cells. Cisplatin and RA monotherapy, but not combination significantly inhibited HNSCC cell migration.

This study found that cisplatin-RA combination can inhibit proliferation and induce apoptosis in HNSCC cell lines.

Cisplatin and rosmarinic acid combination

Cell proliferation

Apoptosis

Migration

Head and neck cancer

© 2025 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.Vé