Copper (II) increases anti-Proliferative activity of thymoquinone in colon cancer cells by increasing genotoxic, apoptotic, and reactive oxygen species generating effects.


Yenigun V. B., Kocyigit A., Kanımdan E., Balkan E., Gul A. Z.

Toxicon : official journal of the International Society on Toxinology, cilt.250, ss.108103, 2024 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 250
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.toxicon.2024.108103
  • Dergi Adı: Toxicon : official journal of the International Society on Toxinology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Environment Index, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.108103
  • Bezmiâlem Vakıf Üniversitesi Adresli: Evet

Özet

Thymoquinone is the main active compound derived from the essential oil of the Nigella sativa plant seed. While thymoquinone is an antioxidant, it has been reported in several studies that thymoquinone has dose-dependent pro-oxidant activity with the Fenton reaction in the presence of transition elements such as iron and copper. This study aimed to investigate cytotoxic, apoptotic, genotoxic, and reactive oxygen species (ROS) generating effects of thymoquinone treated with copper in colon cancer cells. HT-29 cells were treated with pro-oxidant-acting doses of thymoquinone alone and together with the non-toxic dose of Copper (II) Sulfate for 24 h. Cytotoxic, apoptotic, genotoxic, and ROS production activities were analyzed by MTT viability test, Acridine Orange/ Ethidium Bromide (AO/EB) staining, alkaline single cell gel electrophoresis and H2DCF-DA assay, respectively. Viability results showed that thymoquinone and copper synergistically affect cancer cells, and DNA damage was increased with the synergic effect. The intracellular ROS was increased when thymoquinone and copper were applied together. Applying redox-active copper (II) with thymoquinone increases DNA damage, apoptosis, and cell death by increasing the amount of intracellular ROS through pro-oxidant activity. Treatments targeting copper-related pathways may open new therapeutic avenues for cancer treatment.