Differential expression of members of the tumor necrosis factor α-related apoptosis-inducing ligand pathway in prostate cancer cells

S. Sridhar, A. A. Ali, Y. Liang, M. F. El Etreby, R. W. Lewis, M. V. Kumar

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Androgen ablation therapy induces apoptosis only in androgen-sensitive prostate cancer cells; therefore, other cytotoxic drugs are being used to induce apoptosis in androgen-refractory cells. Mifepristone, an antiprogestin used individually or together with the antiestrogen Tamoxifen, has been recommended for induction of cell death and treatment of several hormonal cancers. However, little is known about the mechanism of action of these drugs in prostate cancer. Therefore, we investigated the effect of Mifepristone on the tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL) pathway, a newly identified and very effective member of tumor necrosis factor-α family. Mifepristone and Tamoxifen induced significant expression of death receptors in prostate cancer cells in vitro and in xenografts. However, Mifepristone in combination with Tamoxifen did not increase prostate cancer cell death compared with their individual values. The involvement of the TRAIL pathway was further confirmed by the activation of caspase-8 in Mifepristone-treated cells. This was followed by truncation of Bid, confirming that Mifepristone activates the TRAIL pathway. This knowledge is being used to design a combination treatment of TRAIL and Mifepristone to induce significant apoptosis in prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)7179-7183
Number of pages5
JournalCancer Research
Volume61
Issue number19
StatePublished - Oct 1 2001

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sridhar, S., Ali, A. A., Liang, Y., El Etreby, M. F., Lewis, R. W., & Kumar, M. V. (2001). Differential expression of members of the tumor necrosis factor α-related apoptosis-inducing ligand pathway in prostate cancer cells. Cancer Research, 61(19), 7179-7183.