Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination

Authors

  • U.A. Sanli,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • G. Gorumlu,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • C. Erten,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • M.K. Gul,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • E. Cengiz,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • Y. Kucukzeybek,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • B. Karaca,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • H. Atmaca,

    1. Section of Molecular Biology, Department of Biology, Faculty of Science and Arts, Celal Bayar University, 45140 Muradiye, Manisa, Turkey
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  • S. Uzunoglu,

    1. Section of Molecular Biology, Department of Biology, Faculty of Science and Arts, Celal Bayar University, 45140 Muradiye, Manisa, Turkey
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  • B. Karabulut,

    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
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  • R. Uslu

    Corresponding author
    1. Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey
      Tel.: +90 232 390 39 06; fax: +90 232 374 73 21. E-mail addresses: ruchan.uslu@ege.edu.tr
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Tel.: +90 232 390 39 06; fax: +90 232 374 73 21. E-mail addresses: ruchan.uslu@ege.edu.tr

Abstract

Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer.

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