From inert to bioactive: Titanium surfaces engineered to suppress oral cancer cell proliferation and migration

Chem Biol Interact. 2025 Oct 22:420:111667. doi: 10.1016/j.cbi.2025.111667. Epub 2025 Jul 19.

Abstract

The chemical modification of the titanium implant surface altered the nature of its interactions with the biological environment. A surface was designed that transformed from anticancer-inert to highly anticancer-active against oral squamous cell carcinoma (OSCC) cells. Titanium implants were coated using a combined anodizing/anaphoretic electrodeposition process. The biological effects of coated (Ti/Coating) versus uncoated (Ti) titanium were tested on the SCC-25 cells. Apoptosis, cellular uptake, cell cycle, and intracellular ROS generation were evaluated by flow cytometry. Gene and protein expression levels related to apoptosis (BAX, BCL2, CASP3, CASP8, CASP9), proliferation (Cyclin D1), EMT (VIM, SNAIL, SLUG, CDH1, HDAC 2), and signaling pathways (AKT/mTOR, Wnt/β-catenin) were assessed via qPCR and Western blot. Migration was analyzed through a wound healing assay. The Ti/Coating system significantly reduced cell viability and induced early apoptosis without increasing necrosis. Apoptosis was associated with BAX upregulation and BCL2 downregulation. Cell cycle arrest in G2/M phase was noted. ROS generation was markedly elevated, contributing to cytotoxic effects. Ti/Coating inhibited the expression of EMT-related markers (VIM, SLUG, SNAIL) and upregulated CDH1, correlating with reduced cell migration. Additionally, Ti/Coating downregulated AKT, mTOR, and β-catenin expression, indicating suppression of key oncogenic signaling pathways. The uncoated titanium surface showed no significant effects. The Ti/Coating system had a substantial anticancer effect on oral cancer cells by inducing apoptosis, elevating oxidative stress, and modulating EMT, cell cycle, and oncogenic signaling. These findings highlight its potential as a biologically active implant material for localized postoperative therapy in OSCC, combining structural support with preventive anticancer activity.

Keywords: Chitosan; Coatings-cell interaction; Nano-hydroxyapatite; Oral cancer cells; Selenium; Surface-chemical modification.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Proliferation* / drug effects
  • Coated Materials, Biocompatible* / chemistry
  • Coated Materials, Biocompatible* / pharmacology
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / metabolism
  • Mouth Neoplasms* / pathology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Surface Properties
  • TOR Serine-Threonine Kinases / metabolism
  • Titanium* / chemistry
  • Titanium* / pharmacology

Substances

  • Titanium
  • Reactive Oxygen Species
  • Antineoplastic Agents
  • TOR Serine-Threonine Kinases
  • Coated Materials, Biocompatible