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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
Author(s) -
Ding Haiming,
Han Chunhua,
GibsonD′Ambrosio Ruth,
Steele Ver E.,
D′Ambrosio Steven M.
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11499
Subject(s) - limiting , piroxicam , cancer research , cell growth , medicine , oncology , chemistry , pathology , biochemistry , mechanical engineering , engineering , alternative medicine
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 μM for premalignant and malignant cells, respectively. Piroxicam did not induce apoptosis. The growth inhibitory effect was COX and PGE 2 independent. Adding PGE 2 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 G 2 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. © 2003 Wiley‐Liss, Inc.