| Treatment with the PARP-inhibitor PJ34 causes enhanced doxorubicin-mediated cell death in HeLa cells. | |
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MedLine Citation:
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PMID: 22293659 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Adjuvant therapies can incorporate a number of different drugs to minimize the cardiotoxicity of cancer chemotherapy, decrease the development of drug resistance and increase the overall efficacy of the treatment regime. Topoisomerase IIα is a major target of many commonly used anticancer drugs, where cell death is brought about by an accumulation of double-strand DNA breaks. Poly (ADP-ribose) polymerase (PARP)-1 has been extensively studied for its role in the repair of double-strand DNA breaks, but its ability to add highly negative biopolymers (ribosylation) to target proteins provides a vast number of pathways where it can also be important in mediating cell death. In this study, we combine the classical topoisomerase IIα poison doxorubicin with the PARP inhibitor PJ34 to investigate the potentiation of chemotherapeutic efficiency in HeLa cells. We demonstrate that PJ34 treatment has the capacity to increase endogenous topoisomerase IIα protein by about 20%, and by combining doxorubicin treatment with PJ34, we observed a 50% improvement in doxorubicin-mediated cell death in HeLa cells. These results were correlated with the ribosylation of transcription factor specificity factor 1 after doxorubicin treatment, thereby altering its affinity for binding to known regulatory elements within the human topoisomerase IIα promoter. Taken together, these results highlight the synergistic potential of combining PARP inhibitors with classical topoisomerase IIα-targeting drugs. |
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Authors:
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Natisha Magan; Richard J Isaacs; Kathryn M Stowell |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-29 |
Journal Detail:
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Title: Anti-cancer drugs Volume: - ISSN: 1473-5741 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-2-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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aInstitute of Molecular BioSciences, Massey University, Palmerston North bRegional Cancer Treatment Service, Palmerston North Public Hospital, New Zealand. |
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