Thymoquinone-derived Titanium Nanoparticles Induce Nrf2-mediated Anticancer Activity against KB Cells

Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer with unfavorable therapeutic responses and high recurrence. KB cells are used as a model to investigate OSCC response to new anticancer drugs. Thymoquinone, a phytochemical obtained from Nigella sativa, has high antioxidant and anticancer activities. The purpose of this investigation is the synthesis of titanium nanoparticles based on thymoquinone (TQ-TiNPs) and assessment of their cytotoxicity and antioxidant activity in KB cells with attention towards Nrf2 pathway modulation. TQ-TiNPs were prepared through green chemistry by reducing titanium(IV) isopropoxide using thymoquinone. The nanoparticle characterization was done through UV-Visible spectroscopy, FTIR, XRD, SEM, DLS, and zeta potential analysis. KB cells were treated with TQ-TiNPs at doses of 1, 10, 25, 50, and 100 µg/mL, and the cytotoxicity was evaluated through MTT assay. The DPPH assay was carried out to measure antioxidant activity. The gene expression of Nrf2, Keap1, HO-1, NQO1, and Caspase-3 was evaluated through quantitative real-time PCR. Characterization identified the development of stable, spherical, and crystalline nanoparticles with 300–400 nm absorbance and <100 nm particle size. TQ-TiNPs inhibited KB cell viability in a dose-dependent manner (p < 0.05). DPPH assay identified robust radical scavenging activity, especially at high concentrations. Gene expression analysis identified upregulation of Nrf2, HO-1, NQO1, and Caspase-3 and downregulation of Keap1, representing activation of antioxidant and apoptotic pathways. Thymoquinone-derived titanium nanoparticles exerted vigorous anticancer activity against KB cells by modulating the Nrf2/Keap1 signalling pathway and inducing apoptosis. The results endorse the promise of TQ-TiNPs as a green nanotherapeutic approach towards oral cancer.