Open Access

17-ABAG, a novel geldanamycin derivative, inhibits LNCaP-cell proliferation through heat shock protein 90 inhibition

  • Authors:
    • Zhiyuan Lin
    • Ruixian Peng
    • Zhenyu Li
    • Yang Wang
    • Chunhua Lu
    • Yuemao Shen
    • Jifeng Wang
    • Guowei Shi
  • View Affiliations

  • Published online on: June 9, 2015     https://doi.org/10.3892/ijmm.2015.2239
  • Pages: 424-432
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Prostate cancer is one of the most common cancer types worldwide. In 2014, there were an estimated 233,000 new cases and 29,480 mortalities in the United States. Androgen deprivation therapy, also called androgen suppression therapy, targets androgen signaling and remains the standard treatment for patients with advanced prostate cancer; however, responses to treatment are not durable and most patients advance to castrate-resistant prostate cancer. Therefore, novel therapeutic strategies to treat prostate cancer are urgently required. Heat shock protein 90 (Hsp90) is a chaperone protein that has been shown to regulate the progression of tumor cells. Numerous Hsp90 inhibitors show anti‑tumor activity and several of them have entered clinical trials. Geldanamycin (GA) was identified as the first Hsp90 inhibitor, but shows hepatotoxicity at its effective concentrations, limiting its clinical use. In previous studies by our group, the GA derivative 17-ABAG was designed and synthesized. The present study showed that 17-ABAG inhibits the proliferation and induces apoptosis of LNCaP, an androgen-dependent prostate cancer cell line, in vitro through a classic apoptotic pathway. 17-ABAG also downregulated the Hsp90 client protein and inhibited androgen receptor nuclear localization in LNCaP cells. In addition, 17-ABAG suppressed the growth of LNCaP xenograft tumors without any obvious side-effects. The present study demonstrated that 17-ABAG is a promising anti‑tumor agent and warrants further validation in prospective studies.
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August-2015
Volume 36 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lin Z, Peng R, Li Z, Wang Y, Lu C, Shen Y, Wang J and Shi G: 17-ABAG, a novel geldanamycin derivative, inhibits LNCaP-cell proliferation through heat shock protein 90 inhibition. Int J Mol Med 36: 424-432, 2015
APA
Lin, Z., Peng, R., Li, Z., Wang, Y., Lu, C., Shen, Y. ... Shi, G. (2015). 17-ABAG, a novel geldanamycin derivative, inhibits LNCaP-cell proliferation through heat shock protein 90 inhibition. International Journal of Molecular Medicine, 36, 424-432. https://doi.org/10.3892/ijmm.2015.2239
MLA
Lin, Z., Peng, R., Li, Z., Wang, Y., Lu, C., Shen, Y., Wang, J., Shi, G."17-ABAG, a novel geldanamycin derivative, inhibits LNCaP-cell proliferation through heat shock protein 90 inhibition". International Journal of Molecular Medicine 36.2 (2015): 424-432.
Chicago
Lin, Z., Peng, R., Li, Z., Wang, Y., Lu, C., Shen, Y., Wang, J., Shi, G."17-ABAG, a novel geldanamycin derivative, inhibits LNCaP-cell proliferation through heat shock protein 90 inhibition". International Journal of Molecular Medicine 36, no. 2 (2015): 424-432. https://doi.org/10.3892/ijmm.2015.2239