Carcinoma cell lines resistant for growth inhibition and apoptosis to retinoic acid are responsive to 4-hydroxy-phenyl-retinamide: Correlation with tissue transglutaminase

Retinoic acid (RA)-resistant cell lines are highly malignant. To inhibit th e growth of the RA-resistant cells we used 4-HPR, a synthetic retinoid, whi ch may act through alternative signal transduction pathways. 4-HPR induced cell growth inhibition and apoptosis in all HA-sensitive as well as -resist ant 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 eig ht RA-sensitive cell lines, However, basal TGase differed in the different cells, suggesting inducibility rather than basal levels as the relevant par ameter. In sharp contrast to the RA-sensitive cells, RA-resistant cells sho wed sporadic response to 4-HPR for tissue TGase, The wider spectrum of acti vity of 4-HPR in inhibiting cell growth and inducing apoptosis makes it a g ood candidate for the treatment of RA-resistant cancer cells.