Abstract：
:The Bcr/Abl tyrosine kinase that is expressed from the Philadelphia chromosome protects leukemia cells from apoptosis caused by removal of growth factors or by cytotoxic agents and ionizing irradiation. This resistance to apoptosis is associated with a Bcr/Abl-mediated G2/M delay. Therefore, inhibiting Bcr/Abl signaling pathways should block the ability of the Bcr/Abl kinase to protect cells from apoptosis. The monoterpenes, limonene and perillyl alcohol (POH) are new anticancer agents that selectively induce apoptosis in neoplastic cells of a variety of rodent carcinoma models. Since the potential antitumor activities of monoterpenes overlap with signaling pathways affected by the Bcr/Abl kinase, POH and limonene were tested for antileukemia activity. POH, but not limonene selectively induced G0/G1 arrest followed by apoptosis in Bcr/Abl-transformed, but not nontransformed FDC.P1 and 32D myeloid cell lines. In contrast to their greater sensitivity to POH, Bcr/Abl-transformed cells were more resistant than nontransformed cells to several chemotherapy agents and ionizing irradiation. Since in Bcr/Abl-transformed cells, POH induces apoptosis associated with G0/G1 arrest, POH must activate an apoptotic pathway that is not protected by the Bcr/Abl-induced G2/M delay. Monoterpenes may represent novel agents for treating Ph+ leukemias.
journal_name
Leukemiajournal_title
Leukemiaauthors
Sahin MB,Perman SM,Jenkins G,Clark SSdoi
10.1038/sj.leu.2401536subject
Has Abstractpub_date
1999-10-01 00:00:00pages
1581-91issue
10eissn
0887-6924issn
1476-5551journal_volume
13pub_type
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