Indomethacin induces apoptosis and inhibits proliferation in chronic myeloid leukemia cells.
A nonsteroidal anti-inflammatory drug (NSAID)--indomethacin (IN), was found to induce apoptosis and inhibit proliferation of K562 cells and primary culture bone marrow cells from six chronic myelogenous leukemia (CML) patients. IN induced cells apoptosis and inhibited cells proliferation in a dose-and time-dependent manner, the optimum IN concentration and incubation time for eliciting these effects were 400 micromol/l and 72 h, respectively. A synergic effect on Vp-16 (2.5 microg/ml) induced apoptosis was observed when combined with 100 micromol/l IN in K562 cells. RT-PCR results showed that IN down-regulated Bcl-2 mRNA expression, and did not change Bax mRNA expression; Western blot results confirmed that IN inhibited Bcl-2 protein expression, no influence was found on the translative level of bax protein. Our study indicate that IN induce apoptosis of CML cells by down-regulating Bcl-2 expression partially, and there is a potential significance in the treatment of CML.
Zhang
G
G
Laboratory of Molecular Hematology, Division of Hematology, The Second Affiliated Hospital, Hunan Medical University, Changsha, Hunan, PR China.
Tu
C
C
Zhang
G
G
Zhou
G
G
Zheng
W
W
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
D000894:Anti-Inflammatory Agents, Non-Steroidal; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007213:Indomethacin