alkaline phosphatase

[Objectives] Recent study on iPS and tumor cells suggests that ALP may be related to the differentiation of cells. Therefore we examined the difference in sensitivity to ALP inhibitors for the purpose of comparing the ALP of non-tumor cells with the tumor cells. [Materials and methods]We measured ALP activity using commercial ALP derived from human bone, small intestine, placenta and liver, and ALPs of human tumor cells, SaOs, Hela, P19 and RA-P19 which was differentiated into neurologic cells treated with retinoic acid (RA). Also, we examined sensitivity of ALP activity to tetramisole, levamisole, L-homoarginine, etidronate and vanadate as ALP inhibitor. [Results and Discussion]The sensitivity to each inhibitor of the ALP activity derived from a human organ varied depending of isozyme type. Sensitivities of the ALP activity derived from human tumor cells did not show the big difference, suggesting that ALP of undifferentiated tumor cells show similar characters regardless of the origin of the organ. The ALP of P19 and RA-P19 showed similar sensitivity to inhibitors except etidronate, but was different for etidronate. Because similar results were obtained with the EDTA, we concluded that etidronate inhibited ALP activity by chelate effects. We examined effects for P19 and RA-P19 ALP activity of Zn, which is necessary for ALP activity. Zn promoted ALP activity with the low concentration, but it inhibited the activity at the high concentration. It was suggested that two kinds of Zn binding sites with low and high affinity were present in P19. Furthermore, we obtained results to suggest that the change of the low affinity site of Zn by the RA treatment caused difference in the sensitivity for etidronate of the ALP activity in P19 and RA-P19. [Conclusion] The change of the Zn binding site which was essential to activity, changed the sensitivity to the inhibitor and that the ALP of tumor cells lost organ-specific sensitivity to inhibitors.