The effect of the polyadenylation inhibitor cordycepin on human Molt-4 and Daudi leukaemia and lymphoma cell lines.
OBJECTIVE
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 antiproliferative and cytotoxic activity via induction of apoptosis, we assessed the effect of cordycepin, a polyadenylation specific 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 Deltapsi(m) reduction, whereas cytotoxicity and cell cycle status were assessed by Trypan blue staining, MTT assay and flow cytometry.


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.
Thomadaki
Hellinida
H
Institute of Biology, NCSR "Demokritos", Aghia Paraskevi Attikis, 15310, Athens, Greece.
Tsiapalis
Chris Milto
CM
Scorilas
Andreas
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007211:Indoles; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009336:Necrosis; D011062:Polynucleotide Adenylyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D005456:Fluorescent Dyes; D007211:Indoles; D013778:Tetrazolium Salts; D013844:Thiazoles; C007293:DAPI; D011062:Polynucleotide Adenylyltransferase; C022616:thiazolyl blue; C058120:cordycepin