Carcinoma cell lines resistant for growth inhibition and apoptosis to retinoic acid are responsive to 4-hydroxy-phenyl-retinamide: correlation with tissue transglutaminase |
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Authors: | MV Chiantore V Giandomenico LM De Luca |
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Affiliation: | Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-4255, USA. |
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Abstract: | Retinoic acid (RA)-resistant cell lines are highly malignant. To inhibit the growth of the RA-resistant cells we used 4-HPR, a synthetic retinoid, which may act through alternative signal transduction pathways. 4-HPR induced cell growth inhibition and apoptosis in all RA-sensitive as well as -resistant cells, demonstrating a wider spectrum of potency over RA. 4-HPR induced tissue TGase activity. A tight correlation between the induction of tissue TGase, the inhibition of cell growth, and apoptosis was evident in all eight RA-sensitive cell lines. However, basal TGase differed in the different cells, suggesting inducibility rather than basal levels as the relevant parameter. In sharp contrast to the RA-sensitive cells, RA-resistant cells showed sporadic response to 4-HPR for tissue TGase. The wider spectrum of activity of 4-HPR in inhibiting cell growth and inducing apoptosis makes it a good candidate for the treatment of RA-resistant cancer cells. |
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