Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line.
Nigella sativa is also known for its properties as a traditional herbal healing for many ailments. In this study, the anticancer properties of thyomquinone (TQ), the active ingredient of N. sativa, were studied using ovarian cancer cell line (Caov-3 cells). The anti-proliferative activity of TQ was determined using MTT and the apoptosis was investigated using Flowcytometry and Annexin-V Assays. Multiparameteric cytotoxicity bioassays were used to quantify the changes in cell permeability and mitochondrial membrane potential. Reactive oxygen species (ROS) and apoptosis-involved cell markers were examined to verify cell death mechanism. The MTT-assay showed that TQ induces anti-proliferative activity on Caov-3 with an IC50 of 6.0±0.03 μg/mL, without any cytotoxic activity towards WRL-68 normal hepatocytes. A significant induction of early phase of apoptosis was shown by annexin-V analysis. Treatment of Caov-3 cells with TQ induces decreases in plasma membrane permeability and mitochondrial membrane potential. Visible decrease in the nuclear area was also observed. A significant decrease is observed in Bcl-2 while Bax is down-regulated. TQ-triggered ROS-mediated has found to be associated with Hsp70 dysregulation, an indicator of oxidative injury. We found that TQ induced anti-cancer effect involves intrinsic pathway of apoptosis and cellular oxidative stress. Our results considered collectively indicated that thyomquinone may be a potential agent for ovarian cancer drug development.
Jazan University Medical Research Centre Jazan Saudi Arabia.
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Taha
Taibah University Al-Moalim MA Bin Ladin (MABL) chair for Scientific Miracles of Prophetic Medicine, College of Medicine Saudi Arabia.
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Sheikh
University of Malaya Department of Pharmacy, Faculty of Medicine KualaLumpur Malaysia.
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Salim
Jazan University Medical Research Centre Jazan Saudi Arabia.
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Mohan
Jazan University Medical Research Centre Jazan Saudi Arabia.
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Khan
University of Malaya Department of Pharmacy, Faculty of Medicine KualaLumpur Malaysia.
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Kamalidehghan
University of Malaya Department of Pharmacy, Faculty of Medicine KualaLumpur Malaysia.
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Ahmadipour
Jazan University Substance Abuse Research Centre Jazan Saudi Arabia siddigroa@yahoo.com.
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Abdelwahab
D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D031881:Nigella sativa / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; C003466:thymoquinone