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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Article

MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro

  • Authors:
    • Patrick Imesch
    • Anouk Goerens
    • Daniel Fink
    • André Fedier
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, University Hospital Zurich, CH-8091 Zurich, Switzerland
  • Pages: 441-444
    |
    Published online on: December 1, 2011
       https://doi.org/10.3892/ol.2011.504
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Abstract

Cordycepin (3'-deoxyadenosine) is an inhibitor of poly(A) polymerase (PAP), an enzyme crucial to mRNA 3'-end processing, which produces the shortening of poly(A) tails, leading to the destabilization of mRNAs. Cordycepin inhibits proliferation and induces apoptosis in tumor cells, indicating its antitumor activity. Defective 3'-end processing is associated with hypersensitivity to UV treatment. We investigated the effects of cordycepin on proliferation and apoptosis in MLH1‑deficient and MLH1-proficient HCT116 colon tumor cells. MLH1 is a DNA mismatch repair (MMR) protein involved in the processing of damaged DNA. Cells with defective MMR show resistance to certain anticancer drugs. The results showed that MLH1-deficient HCT116 cells are 2-fold less sensitive to the cytostatic effect of cordycepin, as compared to MLH1-proficient cells. This reduced sensitivity to cordycepin in MLH1-deficient cells was associated with reduced upregulation of the cell cycle inhibitor p21. MLH1-deficient cells also exhibited reduced susceptibility to apoptosis upon treatment with cordycepin, as demonstrated by the reduced PARP-1 cleavage. Our findings showed that MLH1-deficient HCT116 colon tumor cells are resistant to the cytostatic and cytotoxic effect of cordycepin, indicating a possible involvement of MMR in mRNA polyadenylation. The findings also suggest that cordycepin is not suitable to therapeutically encounter tumor cells lacking MLH1 expression.
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Copy and paste a formatted citation
Spandidos Publications style
Imesch P, Goerens A, Fink D and Fedier A: MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro. Oncol Lett 3: 441-444, 2012.
APA
Imesch, P., Goerens, A., Fink, D., & Fedier, A. (2012). MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro. Oncology Letters, 3, 441-444. https://doi.org/10.3892/ol.2011.504
MLA
Imesch, P., Goerens, A., Fink, D., Fedier, A."MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro". Oncology Letters 3.2 (2012): 441-444.
Chicago
Imesch, P., Goerens, A., Fink, D., Fedier, A."MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro". Oncology Letters 3, no. 2 (2012): 441-444. https://doi.org/10.3892/ol.2011.504
Copy and paste a formatted citation
x
Spandidos Publications style
Imesch P, Goerens A, Fink D and Fedier A: MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro. Oncol Lett 3: 441-444, 2012.
APA
Imesch, P., Goerens, A., Fink, D., & Fedier, A. (2012). MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro. Oncology Letters, 3, 441-444. https://doi.org/10.3892/ol.2011.504
MLA
Imesch, P., Goerens, A., Fink, D., Fedier, A."MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro". Oncology Letters 3.2 (2012): 441-444.
Chicago
Imesch, P., Goerens, A., Fink, D., Fedier, A."MLH1-deficient HCT116 colon tumor cells exhibit resistance to the cytostatic and cytotoxic effect of the poly(A) polymerase inhibitor cordycepin (3'-deoxyadenosine) in vitro". Oncology Letters 3, no. 2 (2012): 441-444. https://doi.org/10.3892/ol.2011.504
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