Carcinoma Cell Lines Resistant for Growth Inhibition and Apoptosis to Retinoic Acid Are Responsive to 4-Hydroxy-phenyl-retinamide: Correlation with Tissue Transglutaminase

• Published in: Biochemical and biophysical research communications Vol. 254; no. 3; pp. 636 - 641
• Main Authors: Chiantore, Maria V., Giandomenico, Valeria, De Luca, Luigi M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.01.1999
• Subjects: 3T3 Cells; Animals; Apoptosis - drug effects; Carcinoma - enzymology; Carcinoma - pathology; Cell Division - drug effects; Fenretinide - pharmacology; Humans; Mice; Transglutaminases - metabolism; Tretinoin - pharmacology; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.9987

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.