Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Apoptosis induction in prostate cancer cells by a novel gene product, pHyde, involves caspase-3

Oncogene volume 20, pages 5982–5990 (2001)Cite this article

Abstract

A novel gene, pHyde, was recently cloned from Dunning rat prostate cancer cells. A recombinant adenovirus containing pHyde cDNA gene (AdpHyde) was generated to investigate the biological function of pHyde protein. AdpHyde inhibited the growth of human prostate cancer cells. Apoptosis was induced in AdpHyde transduced cells as demonstrated by DAPI (4′, 6-diamino-2-phenylindole), TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) staining, and flow cytometry assays. Apoptosis was also induced in human xenograft prostate cancer tumors growing in nude mice following treatment with AdpHyde. AdpHyde transduction resulted in a dose-dependent stimulation of caspase-3 activity in DU145 cells which was blocked by DEVD (succinyl-Asp-Glu-Val-Asp-aldehyde) and VAD (benzyloxycarbonyl - Val - Ala - Asp -fluoromethylketone), inhibitors specifically against caspase-3. Moreover, cancer cells that lacked expression of endogenous caspase-3 were not or barely inhibited by pHyde. These results taken together suggest that pHyde inhibits cancer growth by inducing apoptosis through a caspase-3 dependent pathway.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  • Buckley CD, Pilling D, Henriguez NV, Parsonage G, Threlfall K, Scheel-Toellner D, Simmons DL, Akbar AN, Lord JM, Salmon M . 1999 Nature 397: 534–539

  • Carter BH, Piantadosi S, Isaacs JT . 1990 J. Urol. 143: 742–746

  • Chang H, Yang X . 2000 Microbiol. Mol. Biol. Rev. 64: 821–846

  • Cohen GM . 1997 Biochem. J. 326: 1–16

  • Duan H, Chinnaiyan AM, Hudson PL, Wing JP, He W-W, Dixit VM . 1996 J. Biol. Chem. 271: 1621–1625

  • Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S . 1998 Nature 391: 43–50

  • El-Etreby MF, Liang Y, Wrenn RW, Schoenlein PV . 1998 Breast Cancer Res. Treat 51: 149–168

  • Graham FL, Prevec L . 1991 Methods in Molecular Biology Murray EJ (ed.) Human Press Inc Chapter 11 pp 109–128

    Google Scholar 

  • Greenlee RT, Hill-Harmon MB, Murray T, Thun M . 2001 CA Cancer J. Clin. 51: 15–36

  • Hyer ML, Rubinchik S, Dong J-Y, Voelkel-Johnson C, Gunhan M, Norris JS . 2000 Mol. Ther. 1: S322

  • Jackman J, O'Connor PM . 1998 Current Protocols in Cell Biology. Bonifacino JS, Dasso M, Harford JB . Lippincott-Schwartz and Yamada KM (eds.) John Wiley & Sons, Inc pp 8.3.1–8.3.16

    Google Scholar 

  • Janicke RU, Walker PA, Lin XY, Porter AG . 1996 EMBO J. 15: 6969–6978

  • Janicke RU, Sprengart ML, Wati MR, Porter AG . 1998 J. Biol. Chem. 273: 9357–9360

  • Kadkol SS, Brody JR, Epstein JI, Kuhajda FP, Pasternack GR . 1998 Prostate 34: 231–237

  • Li F, Srinivasan A, Wang Y, Armstrong RC, Tomaselli KJ, Fritz LC . 1997 J. Biol. Chem. 272: 30299–30305

  • Liu X, Zou H, Slaughter C, Wang X . 1997 Cell 89: 175–184

  • Lu Y, Whitaker L, Li X, Lotan D, Lotan R . 1995 Mol. Cell. Differ. 3: 175–191

  • Lu Y, Carraher J, Zhang Y, Armstrong J, Lerner J, Roger W, Steiner MS . 1999 Cancer Gene Ther. 6: 64–72

  • Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami H-O . 1997 Br. J. Cancer 76: 1115–1118

  • Nicholson DW, Thornberry NA . 1997 Trends Biochem. Sci. 22: 299–306

  • Oberhammer F, Wilson JW, Dive C, Morris ID, Hickman JA, Wakeling AE, Walker PR, Sikorska M . 1993 EMBO J. 12: 3679–3684

  • Okuma E, Saeki K, Shimura M, Ishizaka Y, Yasug E, You A . 2000 Leukemia 14: 612–619

  • Oridate N, Lotan D, Xu X-C, Hong WK, Lotan R . 1996 Clin. Cancer Res. 2: 855–863

  • Porter AG, Ng P, Janicke RU . 1997 BioEssays 19: 501–507

  • Rinaldy A, Steiner MS . 1999 DNA Cell Biol. 18: 829–836

  • Rokhlin OW, Bishop GA, Hostager BS, Waldschmidt TJ, Sidorenko SP, Pavloff N, Kiefer MC, Umansky SR, Glover RA, Cohen MB . 1997 Cancer Res. 57: 1758–1768

  • Sakahira H, Enari M, Nagata S . 1998 Nature 391: 96–99

  • Sandberg AA . 1992 Hum. Pathol. 23: 368–380

  • Schulze-Osthoff K, Walczak H, Droge W, Krammer PH . 1994 J. Cell. Biol. 127: 15–20

  • Steiner MS, Zhang X, Wang Y, Lu Y . 2000 Cancer Res. 60: 4419–4425

  • Stennicke HR, Salvesen GS . 1998 Biochim. Biophys. Acta. 1387: 17–31

  • Stennicke HR, Jurgensmeier JM, Shin H, Deveraux Q, Wolf BB, Yang X, Zhou Q, Ellerby HM, Ellerby LM, Bredesen D, Green DR, Reed JC, Froelich CJ, Salvesen GS . 1998 J. Biol. Chem. 273: 27084–27090

  • Talanian RV, Yang X, Turbov J, Seth P, Ghayur T, Casiano CA, Orth K, Froelich CJ . 1997 J. Exp. Med. 186: 1323–1331

  • Tewari M, Quan LT, O'Rourke K, desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM . 1995 Cell. 81: 801–809

  • Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J, Elliston KO, Ayala JM, Casano FJ, Chin J, Ding GJ-F, Egger LA, Gaffney EP, Limjuco G, Palyha OC, Raju SM, Rolando AM, Salley JP, Yamin TT, Lee TD, Shively JE, MacCross M, Mumford RA, Schmidt JA, Tocci MJ . 1992 Nature 356: 768–774

  • Tseng CP, Ely BD, Li Y, Pong RC, Hsieh JT . 1998 Endocrinol. 139: 3542–3553

  • Ucker DS, Obermiller PS, Eckhart W, Apgar JR, Berger NA, Meyers J . 1992 Mol. Cell. Biol. 12: 3060–3069

  • Wolk A, Mantzoros CS, Andersson S-O, Bergstrom R, Signorello LB, Lagiou P, Adami HO, Trichopoulos D . 1998 J. Natl. Cancer Inst. 90: 876–879

  • Yang X, Stennicke HR, Wang B, Green DR, Janicke RU, Srinicasan A, Seth P, Salvesen GS, Froelich CJ . 1998 J. Biol. Chem. 273: 34278–34283

  • Zhang XW, Qing C, Xu B . 1999 Anticancer Drugs 10: 569–576

Download references

Acknowledgements

This research was supported in part by University of Tennessee Medical Group Morenton Oncology Research Grant and American Cancer Society Grant #IRG-87-008-09, and in part by Assisi Foundation of Memphis and Hyde Family Foundation. The cost of publication was supported by University of Tennessee Vascular Biology Center of Excellence Partnership Grant.

Author information

Authors and Affiliations

  1. Department of Urology, University of Tennessee Health Science Center, Memphis, TN 38163, Tennessee, USA

    Xiongwen Zhang, Mitchell S Steiner, Augustinus Rinaldy & Yi Lu

Authors
  1. Xiongwen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitchell S Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Augustinus Rinaldy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi Lu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, X., Steiner, M., Rinaldy, A. et al. Apoptosis induction in prostate cancer cells by a novel gene product, pHyde, involves caspase-3. Oncogene 20, 5982–5990 (2001). https://doi.org/10.1038/sj.onc.1204831

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204831

Keywords

This article is cited by

Search

Advanced search

Quick links