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

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Abstract

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. Induction of apoptosis was determined by endonucleosomal DNA cleavage, DAPI staining, caspase-6 activity assay and ΔΨm 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 PAP changes in all cell lines, in response to apoptosis induced by etoposide, in many cases even prior to hallmarks of apoptosis (endonucleosomal cleavage of DNA, ΔΨm reduction). A further elucidation to this apoptosis–polyadenylation correlation was added, by cell treatment with cordycepin, resulting in either suppression (U937, K562) or induction (HL-60) of the apoptotic process, according to the cell type. However, inhibition of polyadenylation did not influence the cell lines Daudi and Molt-4 used, where alternative apoptotic pathways are induced through cleavage of DNA into high molecular weight fragments.

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Acknowledgments

This work was supported in part by EU Grant ERBFM RXCT-960096 to C.M.T. We thank Dr. G. Martin from Dr Keller’s Laboratory, Biozentrum, Basel University, Switzerland for the generous gift of PAP polyclonal antiserum, as well as Dr. A. Eastman for helpful advice and the protocol of DNA laddering. We also thank Dr. D. Kletsas and Dr. H. Pratsinis for technical advices, helpful discussions and the use of the flow cytometer.

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Authors and Affiliations

  1. Institute of Biology, NCSR “Demokritos”, Aghia Paraskevi Attikis, 15310, Athens, Greece

    Hellinida Thomadaki & Maria Havredaki

  2. Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701, Athens, Greece

    Hellinida Thomadaki & Andreas Scorilas

  3. Department of Biochemistry and Molecular Biology, Papanikolaou Cancer Research Center, “St Savas” Hospital, 171 Alexandras Avenue, Athens, 11522, Greece

    Chris Milto Tsiapalis

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  1. Hellinida Thomadaki
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  2. Andreas Scorilas
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  3. Chris Milto Tsiapalis
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  4. Maria Havredaki
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Correspondence to Andreas Scorilas.

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Thomadaki, H., Scorilas, A., Tsiapalis, C.M. et al. The role of cordycepin in cancer treatment via induction or inhibition of apoptosis: implication of polyadenylation in a cell type specific manner. Cancer Chemother Pharmacol 61, 251–265 (2008). https://doi.org/10.1007/s00280-007-0467-y

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