Thymoquinone potentiates anti-cancer effects of cisplatin in oral squamous cell carcinoma via targeting oxidative stress

Chem Biol Drug Des. 2024 Mar;103(3):e14492. doi: 10.1111/cbdd.14492.

Abstract

Recent evidence has proved that thymoquinone as a natural polyphenol has great anticancer and anti-proliferative effects in cancer cells. In this study, we aimed to examine the effects of thymoquinone on increasing cisplatin-induced apoptosis human oral squamous cell carcinoma cells and its underlying molecular mechanisms. SCC-25 cancer cells treated by thymoquinone and cisplatin with different concentrations. Cell viability will determine by using MTT assay. The concentrations of reactive oxygen species (ROS) and antioxidant activities were determined using specific related kits. DNA damage, lipid, and protein oxidation were assessed. Real-time PCR and Western blot analysis will be used to determine the expression of apoptosis-related proteins including Bax, Bcl-2, and caspase-3. Combination of thymoquinone and cisplatin suppressed synergistically SCC-25 cancer cell viability and induced apoptosis in dose-depended manner. Cell treatment with combination of thymoquinone and cisplatin led to accumulation of ROS within cells and increase in the intracellular levels of DNA damage, protein and lipid peroxidation. In addition, the combination of thymoquinone and cisplatin modulated the mRNA and protein expression levels of apoptosis-related proteins including Bax, Bcl-2, and caspase-3. Thymoquinone potentiated cisplatin anti-cancer effect on OSCC by inducing oxidative stress in cells.

Keywords: DNA damage; Oral cancer; apoptosis; chemotherapy.

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Benzoquinones*
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / drug therapy
  • Oxidative Stress
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Squamous Cell Carcinoma of Head and Neck
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Cisplatin
  • Caspase 3
  • thymoquinone
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Apoptosis Regulatory Proteins
  • Benzoquinones