title: Chemopreventive and therapeutic potentials of thymoquinone in HepG2 cells: mechanistic perspectives.
abstract: Liver cancer is the fifth commonest malignancy worldwide and the third leading cause of death. Identifying novel curative and preventive therapy may improve its prognosis. In this study, thymoquinone (TQ), the most active biological ingredient of Nigella sativa Linn, was investigated for its antitumor activity. Mechanistic perspectives underlying this antitumor activity were explored by testing its effect on cell cycle, apoptosis, and angiogenesis. In addition, the chemopreventive effect of TQ was carried out by measuring its effect on phase I CYP1A1 and phase II glutathione S-transferase (GST) drug-metabolizing enzymes. The results of the present study revealed the effectiveness of TQ as an antitumor agent against different types of cancer including brain, colon, cervix and liver at both a time- and concentration-dependent manner. In HepG2 cells, it induced G2/M phase cell cycle arrest and a concentration-dependent increase in the percentage of apoptotic cells with an increase in the ratio of Bax/BCL-2. Moreover, the expression of mRNA and protein level of vascular endothelial growth factor decreased as the concentration of TQ increased. Our data showed a significant inhibition of induced phase I CYP1A1 enzyme, and elevation in the content of glutathione and activity of phase II enzyme GST, in HepG2 cells. Our results provide support for the beneficial use of TQ as a therapeutic and chemopreventive agent against liver cancer.
authors: Pharmacology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt.
authors: Abeer
authors: A
authors: ElKhoely
authors: Hafez F
authors: HF
authors: Hafez
authors: Abeer M
authors: AM
authors: Ashmawy
authors: Osama
authors: O
authors: Badary
authors: Ahmed
authors: A
authors: Abdelaziz
authors: Adel
authors: A
authors: Mostafa
authors: Samia A
authors: SA
authors: Shouman
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D016227:Benzoquinones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D005978:Glutathione; C003466:thymoquinone