The effect of the polyadenylation inhibitor cordycepin on human Molt-4 and Daudi leukaemia and lymphoma cell lines.

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 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.

The role of cordycepin in cancer treatment via induction or inhibition of apoptosis: implication of polyadenylation in a cell type specific manner.

Purpose: Most anticancer drugs show their antiproliferative and cytotoxic activity via induction of apoptosis. In the present study we assessed the implication and role of cordycepin, a polyadenylation-specific inhibitor and a well-known chemotherapeutic drug, in apoptosis, induced by the anticancer drug etoposide.

Methods: For this purpose, a variety of leukemia and lymphoma cell lines (U937, K562, HL-60, Daudi, Molt-4) were treated with the anticancer drugs etoposide and/or cordycepin and assessed for poly(A) polymerase (PAP) activity and isoforms by the highly sensitive PAP activity assay and western blotting, respectively.

Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction.

Cancer results from an imbalance between cell cycle progression and apoptosis. Therefore, most anticancer drugs exert their antiproliferative and cytotoxic activity via cell cycle arrest and induction of apoptosis, a controlled form of cell death that is dysregulated in cancer. Many polyadenylation trans-acting factors, including polyadenylate polymerase (PAP), are increasingly found to be involved in cell cycle, apoptosis and cancer prognosis.

PAP modulations in Daudi cells and Molt-3 cells treated with etoposide are mutually associated with morphological evidence of apoptosis.

Daudi (B-cell line) and Molt-3 (T-cell line) cells provide a model for the study of apoptosis, the induction of which is often accompanied by concominant modulations of proteins involved in mRNA maturation. One of these proteins is poly(A) polymerase (PAP), which is responsible for mRNA cleavage and polyadenylation. A number of recent reports also suggest involvement of mRNA maturation and stability in the induction of specific pathways of cell apoptosis.

C-MYC and IGF-II mRNA-binding protein (CRD-BP/IMP-1) in benign and malignant mesenchymal tumors.

Mouse coding region determinant-binding (mCRD-BP) and human IGF-II mRNA-binding 1 (hIMP-1) proteins are orthologous mRNA-binding proteins that recognize c-myc and IGF-II mRNA, respectively, and regulate their expression posttranscriptionally. Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA and that it is predominantly expressed in fetal tissues. Moreover, hCRD-BP/IMP-1 expression was detected in cell lines of neoplastic origin and in selected primary tumors.