In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone.
Thymoquinone (TQ) is likely responsible for the chemotherapeutic effects of N. sativa extract; however, the cellular mechanisms remain ill-defined. TQ-induced cytotoxicity was investigated using canine osteosarcoma (COS31), its cisplatin-resistant variant (COS31/rCDDP), human breast adenocarcinoma (MCF7), human ovarian adenocarcinoma (BG-1) and Madin-Darby canine (MDCK) cell lines. TQ-induced cytotoxicity was determined using a proliferation assay (MTT assay) and apoptosis assays. Effects of TQ on the cell cycle were determined using flow cytometry. COS31/rCDDP resistant cells were the most sensitive cell line to TQ and MDCK cells were the least sensitive. TQ (25 micro M) induced apoptosis of COS31 cells 6 h after treatment and decreased the number of COS31 cells in S-phase and increased cells in G1-phase, indicating cell cycle arrest at G1. These results suggest that TQ kills cancer cells by a process that involves apoptosis and cell cycle arrest. Non-cancerous cells are relatively resistant to TQ.
Shoieb
Ahmed M
AM
Department of Pathology, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996-4543, USA.
Elgayyar
Mona
M
Dudrick
Paul S
PS
Bell
John L
JL
Tithof
Patricia K
PK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016227:Benzoquinones; D005982:Glutathione Transferase; C003466:thymoquinone; D002945:Cisplatin