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Molecular Pharmacology

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Research ArticleArticle

Induction of Apoptosis byN-(4-Hydroxyphenyl)retinamide and Its Association with Reactive Oxygen Species, Nuclear Retinoic Acid Receptors, and Apoptosis-Related Genes in Human Prostate Carcinoma Cells

Shi-Yong Sun, Ping Yue and Reuben Lotan
Molecular Pharmacology March 1999, 55 (3) 403-410;
Shi-Yong Sun
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Ping Yue
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Reuben Lotan
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Abstract

The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has been shown to induce apoptosis in various malignant cells including human prostate carcinoma cells (HPC). We examined several possible mechanisms by which 4HPR could induce apoptosis in HPC cells. 4HPR exhibited concentration- and time-dependent decrease in cell number both in androgen-dependent (LNCaP) and -independent (DU145 and PC-3) cells. The 4HPR concentrations causing 50% decrease in cell number in LNCaP, DU145, and PC-3 cultures were 0.9 ± 0.16, 4.4 ± 0.45, and 3.0 ± 1.0 μM, respectively, indicating that LNCaP cells were more sensitive to 4HPR than the other cells. 4HPR-induced apoptosis in all three cell lines was evidenced by increased enzymatic labeling of DNA breaks and formation of a DNA ladder. 4HPR increased the level of reactive oxygen species, especially in LNCaP cells. 4HPR-induced apoptosis could be suppressed in LNCaP cells by antioxidant and in DU145 cells by a nuclear retinoic acid receptor-specific antagonist, suggesting the involvement of reactive oxygen species or retinoic acid receptors in mediating apoptosis induced by 4HPR in the different HPC cells. Furthermore, 4HPR modulated the expression levels of some apoptosis-related gene (p21, c-myc, and c-jun), which may also contribute to the induction of apoptosis by 4HPR in HPC cells.

Footnotes

  • Send reprint requests to: Dr. Shi-Yong Sun or Dr. Reuben Lotan, Department of Thoracic/Head and Neck Medical Oncology, Box 108, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. E-mail: ssun{at}notes.mdacc.tmx.edu orrlotan{at}notes.mdacc.tmc.edu

  • This study was supported by a grant from The Prostate Cancer Research Program, University of Texas M. D. Anderson Cancer Center.

  • Abbreviations:
    4HPR
    N-(4-hydroxyphenyl)retinamide
    ATRA
    all-trans-retinoic acid
    HPC
    human prostate cancer
    ROS
    reactive oxygen species
    RARs
    retinoic acid receptors
    RXRs
    retinoid X receptors
    REs
    response elements
    BHA
    butylated hydroxyanisole
    DCF-DA
    2′, 7′-dichlorofluorescin diacetate
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    • Received September 18, 1998.
    • Accepted December 14, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 55 (3)
Molecular Pharmacology
Vol. 55, Issue 3
1 Mar 1999
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Research ArticleArticle

Induction of Apoptosis byN-(4-Hydroxyphenyl)retinamide and Its Association with Reactive Oxygen Species, Nuclear Retinoic Acid Receptors, and Apoptosis-Related Genes in Human Prostate Carcinoma Cells

Shi-Yong Sun, Ping Yue and Reuben Lotan
Molecular Pharmacology March 1, 1999, 55 (3) 403-410;

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Research ArticleArticle

Induction of Apoptosis byN-(4-Hydroxyphenyl)retinamide and Its Association with Reactive Oxygen Species, Nuclear Retinoic Acid Receptors, and Apoptosis-Related Genes in Human Prostate Carcinoma Cells

Shi-Yong Sun, Ping Yue and Reuben Lotan
Molecular Pharmacology March 1, 1999, 55 (3) 403-410;
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