Piroxicam selectively inhibits the growth of premalignant and malignant human oral cell lines by limiting their progression through the S phase and reducing the levels of cyclins and AP-1.
Studies have shown that nonsteroidal antiinflammatory drugs (NSAIDs) reduce the risk of and mortality from a variety of cancers. Although cyclooxygenase (COX)-dependent and -independent pathways may be involved, the mechanisms responsible for these effects remain unknown. In our study, we found that piroxicam inhibited cell growth in premalignant and malignant, but not normal, human oral epithelial cell lines in a concentration- and time-dependent manner. After 6 days of exposure, the concentration that inhibited growth by 50% was 181 and 211 microM for premalignant and malignant cells, respectively. Piroxicam did not induce apoptosis. The growth inhibitory effect was COX and PGE2 independent. Adding PGE2 or infecting cells with a COX-1 transgene did not abrogate piroxicam-induced growth inhibition. After treatment of the premalignant and malignant cell lines with piroxicam, cells accumulated in the S phase of the cell cycle. Upon removal of piroxicam, cells entered the G2 phase. The S phase block was accompanied by a reduction in the protein levels of cyclin A, cyclin B1, cyclin D1, cdc2, PCNA and the c-jun AP-1 component. Therefore, piroxicam may exert its growth inhibitory effects selectively on the premalignant and malignant human oral epithelial cells lines via signaling pathways regulating the progression of cells through the S phase of the cell cycle.
Ding
Haiming
H
Department of Radiology, The Ohio State University, Columbus, OH, USA.
Han
Chunhua
C
Gibson-D'Ambrosio
Ruth
R
Steele
Vernon E
VE
D'Ambrosio
Steven M
SM
D001483:Base Sequence; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017931:DNA Primers; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects; D009062:Mouth Neoplasms / Q000473:pathology*; D010894:Piroxicam / Q000494:pharmacology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D010894:Piroxicam; D001973:Bromodeoxyuridine; D015232:Dinoprostone