The administration schedule of cyclin-dependent kinase inhibitor gene therapy and etoposide chemotherapy is a major determinant of cytotoxicity.

N. S. Prabhu, K. Somasundaram, H. Tian, G. H. Enders, K. Satyamoorthy, M. Herlyn, W. S. El-Deiry

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Cyclin-dependent kinase inhibitors are potent suppressors of cell growth and have been proposed as targets for gene replacement therapy in cancer. Expression of either p16INK4a or p21WAF1 protected cells from the cytotoxic effects of the topoisomerase II inhibitor, etoposide. A lower level of p53 was induced in CDK inhibitor-expressing etoposide-exposed cells suggesting that protection may be due to lower levels of DNA damage in the growth arrested cells. Exposure of human osteosarcoma cells to either p16INK4a or p21WAF1 prior to and during etoposide therapy protected cells against etoposide-induced cell death. Infection of the cells by Ad-p16INK4a or Ad-p21WAF1 following exposure to etoposide resulted in loss of the protective effect with evidence of enhanced growth inhibition. The results suggest that the schedule of administration of DNA damaging etoposide chemotherapy and cell cycle inhibitory therapy is a major determinant of the resulting cytotoxicity.

    Original languageEnglish
    Pages (from-to)209-216
    Number of pages8
    JournalInternational Journal of Oncology
    Volume15
    Issue number2
    Publication statusPublished - 08-1999

    Fingerprint

    Cyclin-Dependent Kinases
    Etoposide
    Genetic Therapy
    Appointments and Schedules
    Drug Therapy
    Growth
    Topoisomerase II Inhibitors
    Cytoprotection
    Osteosarcoma
    Cell- and Tissue-Based Therapy
    DNA Damage
    Cell Cycle
    Cell Death
    DNA
    Infection
    Neoplasms

    All Science Journal Classification (ASJC) codes

    • Cancer Research
    • Oncology

    Cite this

    Prabhu, N. S. ; Somasundaram, K. ; Tian, H. ; Enders, G. H. ; Satyamoorthy, K. ; Herlyn, M. ; El-Deiry, W. S. / The administration schedule of cyclin-dependent kinase inhibitor gene therapy and etoposide chemotherapy is a major determinant of cytotoxicity. In: International Journal of Oncology. 1999 ; Vol. 15, No. 2. pp. 209-216.
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    The administration schedule of cyclin-dependent kinase inhibitor gene therapy and etoposide chemotherapy is a major determinant of cytotoxicity. / Prabhu, N. S.; Somasundaram, K.; Tian, H.; Enders, G. H.; Satyamoorthy, K.; Herlyn, M.; El-Deiry, W. S.

    In: International Journal of Oncology, Vol. 15, No. 2, 08.1999, p. 209-216.

    Research output: Contribution to journalArticle

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