Veratricplatin inhibits the progression of hypopharyngeal squamous cell carcinoma FaDu cells in vitro and in vivo

• DOI: 10.1007/s00280-023-04560-5
• Publication Date: 2023-07-11T06:02:07Z
• Authors: Dongbo Wang; Huina Wu; Qian Wu; Qi Liu; Yamei Li; Jiyong Wu; Jing Nie
• Keywords: Mice; Cyclooxygenase 2 Inhibitors; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Cell Line, Tumor; Animals; Mice, Nude; Apoptosis; 3. Good health

Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer. In recent years, the modification of platinum(II) into platinum(IV) derivative compounds, by introducing biologically active molecules, has been extensively employed to develop novel platinum-based prodrugs. We investigated the anti-proliferative activity against HNSCC of a new veratric acid (COX-2 inhibitor)-platinum(IV) complex.In this study, a new veratric acid (COX-2 inhibitor)-platinum(IV) complex, termed veratricplatin, was synthesized. We evaluated the anti-tumor effect of in vitro and in vivo by western blotting, flow cytometry and DNA damage analysis.Veratricplatin displayed remarkable anti-proliferative activity against various cancer cell lines, including A549, FaDu, HeLa, and MCF-7. Furthermore, veratricplatin demonstrated significantly stronger cytotoxicity than either platinum(II) or veratric acid monotherapy or their combination. Importantly, the synthesized prodrug exhibited less toxicity toward normal cells (MRC-5), while dramatically enhanced DNA damage in FaDu cells inducing apoptosis. Moreover, veratricplatin markedly reduced the migration ability of FaDu cells compared to the control or monotherapy. In vivo, veratricplatin displayed potent anti-tumor activity with no apparent toxicity in BALB/c nude mice bearing FaDu tumors. In addition, tissue immunofluorescence analysis revealed that veratricplatin could substantially inhibit the formation of tumor blood vessels.Veratricplatin demonstrated remarkable drug efficacy, in terms of increased cytotoxicity in vitro and high efficiency with low toxicity in vivo.