Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 61, Issue 4, Pages 703-711Publisher
SPRINGER
DOI: 10.1007/s00280-007-0533-5
Keywords
apoptosis; cell viability; cordycepin; cytotoxicity; PAP; polyadenylation inhibitor
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Purpose Posttranscriptional modifications, such as polyadenylation, are very often implicated in the regulation and dysregulation of cell death, through regulation of the expression of specific genes. Based on the fact that an increasing number of adenosine analogues show their anti-proliferative and cytotoxic activity via induction of apoptosis, we assessed the effect of cordycepin, a polyadenylation speciWc inhibitor, an adenosine analogue and a well-known chemotherapeutic drug, on two human leukemia and lymphoma cell lines. Methods Cells were treated with the anticancer drug cordycepin and assessed for poly(A) polymerase (PAP) activity and isoforms by the highly sensitive PAP activity assay and western blotting, respectively. Induction of apoptosis was determined by endonucleosomal DNA cleavage, DAPI staining and Delta psi(m) reduction, whereas cytotoxicity and cell cycle status were assessed by Trypan blue staining, MTT assay and flow cytometry. Results and conclusions The results showed that the differentiated modulations of PAP in the two cell lines may be a result of the additive effect of the changes in cell cycle and apoptotic pathway induced.
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