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RRR-α-tocopheryl succinate inhibits human prostate cancer cell invasiveness

Oncogene volume 23, pages 3080–3088 (2004)Cite this article

Abstract

RRR-α-tocopheryl succinate (α-vitamin E succinate, VES), one of the vitamin E derivatives, can effectively inhibit the proliferation of human prostate cancer cells. However, little is known about its effect on prostate cancer cell invasive ability. Tumor metastasis is a complex process and the extracellular matrix (ECM) is the first barrier that tumor cells encounter. Therefore, we tested the effect of VES on the invasion of different prostate tumor cells, PC-3, DU-145, and LNCaP, through Matrigel, a reconstituted ECM, using an in vitro cell invasion assay. The invasion of PC-3 and DU-145 cells through Matrigel was inhibited by 20 μ M VES after treating for 24 h. The condition did not alter cell survival, cell cycle, cell adhesion or cell motility. We further investigated whether the ability of VES to inhibit prostate cancer cell invasiveness was associated with its ability to inhibit the activity of matrix metalloproteinases (MMPs), the key enzymes in the proteolysis of basement membrane during invasion. PC-3 and DU-145 cells that were treated with VES showed a significant reduction in the levels of MMP-9 in the culture medium. In contrast, LNCaP cells, which did not secrete MMP-9, were poorly invasive in Matrigel and were hardly affected by treatment with VES. This is the first report suggesting that VES inhibits human prostate cancer cell invasiveness and the reduction of secreted MMP-9 activity could be one of the contributory factors, which points to the potential use of VES in the prevention and therapy of prostate cancer invasion.

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Abbreviations

ECM:

extracellular matrix

ELISA:

enzyme-linked immunoadsorbent assay

FBS:

fetal bovine serum

FCM:

fibroblasts conditioned medium

MMP:

matrix metalloproteinase

PCR:

polymerase chain reaction

RT:

reverse transcription

s.d.:

standard deviation

SDS–PAGE:

sodium dodecyl sulfate polyacrylamide gel electrophoresis

TIMP:

tissue inhibitor of matrix metalloproteinase

α-VE:

α-vitamin E (RRR-α-tocopherol)

VEA:

α-vitamin E acetate (RRR-α-tocopheryl acetate)

VES:

α-vitamin E succinate (RRR-α-tocopheryl succinate)

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Acknowledgements

We are particularly grateful to Drs Chawnshang Chang and Edward M. Messing for helpful discussions. We also thank Xi Na, Karen Wolf, and Susan R. Schoen for manuscript preparation. This work is partly supported by NIH Grant DK60912.

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Authors and Affiliations

  1. Departments of Urology and Pathology, University of Rochester, Rochester, 14642, NY, USA

    Min Zhang, Saleh Altuwaijri & Shuyuan Yeh

  2. Institute of Urology, Peking University, Beijing, PR China

    Min Zhang

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Correspondence to Shuyuan Yeh.

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Zhang, M., Altuwaijri, S. & Yeh, S. RRR-α-tocopheryl succinate inhibits human prostate cancer cell invasiveness. Oncogene 23, 3080–3088 (2004). https://doi.org/10.1038/sj.onc.1207435

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