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.

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.

K562 cell sensitization to 5-fluorouracil- or interferon-alpha-induced apoptosis via cordycepin (3'-deoxyadenosine): fine control of cell apoptosis via poly(A) polymerase upregulation.

K562 cells represent a classical model for the study of drug resistance. Induction of apoptosis is accompanied by concomitant distinct modulations of poly(A) polymerase (PAP) and other proteins involved in mRNA maturation. Recent data suggest the involvement of mRNA stability in the induction of specific apoptosis pathways.

Drug action on poly(A) polymerase activity and isoforms during U937 cell apoptosis.

The enzyme poly(A) polymerase (PAP; EC 2.7.7.

Early 5-fluorouracil-induced changes of poly(A) polymerase in HeLa and WISH cells.

5-Fluorouracil (5-FU), a drug with numerous mechanisms of action which has a long-term suppressive effect on human cancer cell proliferation, mediates both partial dephosphorylation and inactivation of poly(A) polymerase (PAP) [EC. 2.7.