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Methylseleninic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis

Oncogene volume 24, pages 5868–5877 (2005)Cite this article

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytotoxic agent that preferentially induces apoptosis in a variety of human cancer cells. Unfortunately, some tumor cells remain resistant to TRAIL. Therefore, agents that sensitize malignant cells to TRAIL-mediated cell death might be of particular importance for the development of novel antitumor therapeutic regimens. Recent studies establish a critical role of selenium in prostate cancer prevention in vitro and in vivo. Here, we demonstrate that concomitant administration of TRAIL and methylseleninic acid (MSA) produces synergistic effects on the induction of apoptosis in androgen-dependent LNCaP and androgen-independent DU-145 prostate cancer cells. MSA rapidly and specifically downregulates expression of the cellular FLICE inhibitory protein, a negative regulator of death receptor signaling. In addition, we demonstrate that the synergistic effects of MSA and TRAIL result from the activation of the mitochondrial pathway-mediated amplification loop. Addition of MSA effectively blocked TRAIL-mediated BAD phosphorylation at Ser112 and Ser136 in DU-145 cells and was accompanied by induction of the mitochondrial permeability transition and release of apoptogenic cytochrome c and Smac/DIABLO proteins from the mitochondria and into the cytosol. These results suggest that selenium-based dietary compounds may help to overcome resistance to TRAIL-mediated apoptosis in prostate cancer cells.

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References

  • Ashkenazi A and Dixit VM . (1998). Science, 281, 1305–1308.

  • Baker SJ and Reddy EP . (1998). Oncogene, 17, 3261–3270.

  • Boldin MP, Mett IL, Varfolomeev EE, Chumakov I, Shemer-Avni Y, Camonis JH and Wallach D . (1995). J. Biol. Chem., 270, 387–391.

  • Chattopadhyay A, Chiang CW and Yang E . (2001). Oncogene, 20, 4507–4518.

  • Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J and Hood L . (1997). Immunity, 7, 821–830.

  • Chawla-Sarkar M, Bae SI, Reu FJ, Jacobs BS, Lindner DJ and Borden EC . (2004). Cell Death Differ., 11, 915–923.

  • Chen X, Thakkar H, Tyan F, Gim S, Robinson H, Lee C, Pandey SK, Nwokorie C, Onwudiwe N and Srivastava RK . (2001). Oncogene, 20, 6073–6083.

  • Chiang CW, Harris G, Ellig C, Masters SC, Subramanian R, Shenolikar S, Wadzinski BE and Yang E . (2001). Blood, 97, 1289–1297.

  • Chinnaiyan AM, O'Rourke K, Tewari M and Dixit VM . (1995). Cell, 81, 505–512.

  • Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB and Greenberg ME . (2000). Mol. Cell, 6, 41–51.

  • Datta SR, Ranger AM, Lin MZ, Sturgill JF, Ma YC, Cowan CW, Dikkes P, Korsmeyer SJ and Greenberg ME . (2002). Dev. Cell, 3, 631–643.

  • Debatin KM and Krammer PH . (2004). Oncogene, 23, 2950–2966.

  • Deeb D, Jiang H, Gao X, Hafner MS, Wong H, Divine G, Chapman RA, Dulchavsky SA and Gautam SC . (2004). Mol. Cancer Ther., 3, 803–812.

  • Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA and Goodwin RG . (1997). Immunity, 7, 813–820.

  • Dong Y, Ganther HE, Stewart C and Ip C . (2002). Cancer Res., 62, 708–714.

  • Dong Y, Zhang H, Hawthorn L, Ganther HE and Ip C . (2003). Cancer Res., 63, 52–59.

  • Dramsi S, Scheid MP, Maiti A, Hojabrpour P, Chen X, Schubert K, Goodlett DR, Aebersold R and Duronio V . (2002). J. Biol. Chem., 277, 6399–6405.

  • Fulda S and Debatin KM . (2004). Cancer Res., 64, 337–346.

  • Gupta S . (2003). Int. J. Oncol., 22, 15–20.

  • He Q, Rashid A, Rong R, Hillman MJ, Huang Y and Sheikh MS . (2002). Cancer Biol. Ther., 1, 287–290.

  • Henry-Mowatt J, Dive C, Martinou JC and James D . (2004). Oncogene, 23, 2850–2860.

  • Hsu SY, Kaipia A, Zhu L and Hsueh AJ . (1997). Mol. Endocrinol., 11, 1858–1867.

  • Ip C and Ganther HE . (1990). Cancer Res., 50, 1206–1211.

  • Ip C, Hayes C, Budnick RM and Ganther HE . (1991). Cancer Res., 51, 595–600.

  • Ip C, Thompson HJ, Zhu Z and Ganther HE . (2000). Cancer Res., 60, 2882–2886.

  • Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE and Tschopp J . (1997). Nature, 388, 190–195.

  • Jiang C, Wang Z, Ganther H and Lu J . (2001). Cancer Res., 61, 3062–3070.

  • Kataoka T, Schroter M, Hahne M, Schneider P, Irmler M, Thome M, Froelich CJ and Tschopp J . (1998). J. Immunol., 161, 3936–3942.

  • Kim T, Jung U, Cho DY and Chung AS . (2001). Carcinogenesis, 22, 559–565.

  • Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH and Peter ME . (1995). EMBO J., 14, 5579–5588.

  • Kischkel FC, Lawrence DA, Tinel A, LeBlanc H, Virmani A, Schow P, Gazdar A, Blenis J, Arnott D and Ashkenazi A . (2001). J. Biol. Chem., 276, 46639–46646.

  • Klein EA, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR and Coltman C . (2003). Urol. Oncol., 21, 59–65.

  • Korsmeyer SJ, Gross A, Harada H, Zha J, Wang K, Yin XM, Wei M and Zinkel S . (1999). Cold Spring Harb. Symp. Quant. Biol., 64, 343–350.

  • Kroemer G and Reed JC . (2000). Nat. Med., 6, 513–519.

  • Mathas S, Lietz A, Anagnostopoulos I, Hummel F, Wiesner B, Janz M, Jundt F, Hirsch B, Johrens-Leder K, Vornlocher HP, Bommert K, Stein H and Dorken B . (2004). J. Exp. Med., 199, 1041–1052.

  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME and Dixit VM . (1996). Cell, 85, 817–827.

  • Nesterov A, Lu X, Johnson M, Miller GJ, Ivashchenko Y and Kraft AS . (2001). J. Biol. Chem., 276, 10767–10774.

  • Ozoren N and El-Deiry WS . (2002). Neoplasia, 4, 551–557.

  • Ozoren N and El-Deiry WS . (2003). Semin. Cancer Biol., 13, 135–147.

  • Pan G, Ni J, Wei YF, Yu G, Gentz R and Dixit VM . (1997a). Science, 277, 815–818.

  • Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J and Dixit VM . (1997b). Science, 276, 111–113.

  • Saelens X, Festjens N, Walle LV, van Gurp M, van Loo G and Vandenabeele P . (2004). Oncogene, 23, 2861–2874.

  • Scaffidi C, Schmitz I, Krammer PH and Peter ME . (1999). J. Biol. Chem., 274, 1541–1548.

  • Scheid MP, Schubert KM and Duronio V . (1999). J. Biol. Chem., 274, 31108–31113.

  • Srivastava RK . (2001). Neoplasia, 3, 535–546.

  • Taghiyev AF, Guseva NV, Harada H, Knudson CM, Rokhlin OW and Cohen MB . (2003). Mol. Cancer Res., 1, 500–507.

  • Thakkar H, Chen X, Tyan F, Gim S, Robinson H, Lee C, Pandey SK, Nwokorie C, Onwudiwe N and Srivastava RK . (2001). J. Biol. Chem., 276, 38361–38369.

  • Thorburn A . (2004). Cell Signal., 16, 139–144.

  • Venkateswaran V, Klotz LH and Fleshner NE . (2002). Cancer Res., 62, 2540–2545.

  • Voelkel-Johnson C, King DL and Norris JS . (2002). Cancer Gene Ther., 9, 164–172.

  • Walczak H and Krammer PH . (2000). Exp. Cell Res., 256, 58–66.

  • Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC and Lynch DH . (1999). Nat. Med., 5, 157–163.

  • Wang S and El-Deiry WS . (2003). Oncogene, 22, 8628–8633.

  • Wu GS, Burns TF, Zhan Y, Alnemri ES and El-Deiry WS . (1999). Cancer Res., 59, 2770–2775.

  • Zha J, Harada H, Yang E, Jockel J and Korsmeyer SJ . (1996). Cell, 87, 619–628.

  • Zisman A, Ng CP, Pantuck AJ, Bonavida B and Belldegrun AS . (2001). J. Immunother., 24, 459–471.

  • Zu K and Ip C . (2003). Cancer Res., 63, 6988–6995.

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Acknowledgements

This work was supported in part by a tobacco formula grant from the Pennsylvania Department of Health.

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Authors and Affiliations

  1. Department of Urological Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, W329, Philadelphia, 19111, PA, USA

    Kenya Yamaguchi, Robert G Uzzo, Julia Pimkina, Peter Makhov, Konstantin Golovine, Paul Crispen & Vladimir M Kolenko

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  1. Kenya Yamaguchi
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  2. Robert G Uzzo
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Correspondence to Vladimir M Kolenko.

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Yamaguchi, K., Uzzo, R., Pimkina, J. et al. Methylseleninic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis. Oncogene 24, 5868–5877 (2005). https://doi.org/10.1038/sj.onc.1208742

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