Cancer Chemopreventive Retinoids: Validation and Analysis of in Vivo and in Vitro Bioassay Results - Journal of Cancer Therapy

JCT > Vol.7 No.13, December 2016

Cancer Chemopreventive Retinoids: Validation and Analysis of in Vivo and in Vitro Bioassay Results ()

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DOI: 10.4236/jct.2016.713098 1,276 Downloads 2,295 Views Citations

Author(s)

John J. Wille^1,2, Jong Y. Park^1,3, Y. Fulmer Shealy¹

Affiliation(s)

¹Department of Biochemistry, Southern Research Institute, Birmingham, AL, USA.
²Department of Cell Biology, Bioplast Medical, LLC, Chesterfield, NJ, USA.
³Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.

ABSTRACT

Several natural and synthetic retinoids (vitamin-A derived analogies) were examined for their potential anti-cancer activity in both in vivo animal models and a novel in vitro human keratinocyte clonal growth bioassay system. The natural retinoids included all-trans-retinoic (RA), 13-cis-retinoic acid, 4-oxoretinoic acid, and retinol. Among the synthetic retinoids tested were all trans N-(4-hydroxy(phenyl)retinamide, 3-substituted oxoretinoic acids, and 13 cis-N-ethylretinamide. The animal models employed were: 1) vitamin A-deficient hamster tracheal organ assay (HTOC); 2) the benzo(α)pyrene-induced squamous metaplasia in a hamster tracheal organ system (BP-HTOC); 3) the mouse skin tumor promoter (TPA)-induced ornithine decarboxylase enzyme assay(ODC); 4) the mouse skin papilloma (MPA) assay; and 5) a novel retinoid bioassay in which retinoids display IC₅₀ values to inhibit clonal growth of NHK. All-trans-RA, 4-oxoretinoic acid and retinol were consistently more active than any of the synthetic derivatives in all bioassays tested. A statistical model was developed and significant positive correlations were found between: 1) ED₅₀ values in the HTOC system and reduction in TPA-induced ODC enzyme activity; 2) tumors per animal in the MPA bioassay and suppression of TPA-induced ODC activity; and 3) a positive correlation between suppression of tumors per animal in the MPA assay, and retinoid inhibition of keratinocyte clonal growth. Test retinoids, were tested for their capacity to inhibit the clonal growth of a squamous carcinoma cell line (SCC-25), which were found to be 2 - 3 logs less sensitive for each tested retinoid than the corresponding activity against NHK cells. Antineoplastic retinoid drugs were reviewed.

KEYWORDS

Cancer Chemoprevention in Vivo Bioassays, in Vitro Bioassays, Retinoids

Share and Cite:

Wille, J. , Park, J. and Shealy, Y. (2016) Cancer Chemopreventive Retinoids: Validation and Analysis of in Vivo and in Vitro Bioassay Results. Journal of Cancer Therapy, 7, 1008-1033. doi: 10.4236/jct.2016.713098.

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