Therapeutic potential of cyclooxygenase-3 inhibitors in the management of glioblastoma.
In this study we investigated the expression of COX-1, COX-2 and COX-3 mRNA in C6 glioblastoma and normal brain tissues and the effects of acetaminophen, indomethacin or metamizole treatments on the development of C6 glioblastoma in relation with COX inhibition. Glioblastoma cells were inoculated intracerebrally into frontal lobe of adult male Wistar albino rats. 10 days after inoculation, rats were treated with 150 mg/kg acetaminophen, 10 mg/kg indomethacin or 150 mg/kg metamizole. The tumor size was measured histologically and total RNA was isolated from tumor or normal brain tissue and mRNA levels of COX isoforms were determined by qRT-PCR. Our results showed the presence of COX-1, COX-2 and COX-3 expressions in both C6 glioblastoma and normal brain tissues. In tumor tissues COX-3 expression was significantly higher than normal brain tissue (p < 0.05) while there was no significant difference in COX-1 and COX-2 expressions. Acetaminophen and indomethacin decreased the tumor size by 71 and 43 % by inhibiting COX-3 mRNA expression around 87 and 91 % respectively. For the first time our study proposes a possible relationship between COX-3 mRNA expression and C6 glioblastoma development. We also suggested that the inhibition of COX-3 enzyme may be responsible for decrease in tumor size in part, the mechanism by which acetaminophen and indomethacin decreased rat C6 glioblastoma growth. However, the molecular events responsible for COX-3 effects on tumor development are still unresolved as these drugs exert their anti-cancer effect via both COX-3 dependent and independent mechanisms.
Department of Medical Pharmacology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Ersoy
E
Oksuz
Medical Genetics Department, Child Health Institute, Istanbul University, Istanbul, Turkey.
Fatmahan
F
Atalar
Department of Histology and Embryology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Gamze
G
Tanırverdi
Department of Histology and Embryology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Ayahan
A
Bilir
Department of Medical Pharmacology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Andleeb
A
Shahzadi
Department of Medical Pharmacology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. zely@istanbul.edu.tr.
Zeliha
Z
Yazici
D000082:Acetaminophen / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004177:Dipyrone / Q000008:administration & dosage; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D007213:Indomethacin / Q000008:administration & dosage; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D012333:RNA, Messenger; D000082:Acetaminophen; D004177:Dipyrone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; C466421:cyclooxygenase-3; D007213:Indomethacin
Acetaminophen; COX; Glioblastoma; Indomethacin