腫瘍及び非腫瘍細胞由来アルカリ性ホスファターゼの阻害剤に対する反応性の相違

alkaline phosphatase

北海道歯学会

北海道歯学雑誌

[Objectives] In a recent study on iPS and tumor cells, it was suggested that different types of cells have different levels of alkaline phosphatase (ALP) activity. Therefore, we examined differences in sensitivity to ALP inhibitors in both non-tumor cells and tumor cells.[Materials and methods] We measured ALP activity using commercial ALP derived from the small intestine, humanbone, placenta, and liver. ALP activity in human tumor cells: SaOs, Hela, P19, and RA-P19, which was differentiated into neurologic cells with retinoic acid (RA) treatment. Additionally, we examined the sensitivity of ALP activity to inhibitors using tetramisole, levamisole, L-homoarginine, etidronate, and vanadate. [Results and Discussion] The sensitivity to each inhibitor of ALP activity varied depending on the isozyme type and its human organ origin. The sensitivity of ALP activity derived from human tumor cells did not show large differences, suggesting that ALP activity of undifferentiated tumor cells has similar characteristics regardless of the organ origin. ALP activity in P19 and RA-P19 showed similar sensitivity to inhibitors, except for etidronate, which produced different sensitivity. Similar results were obtained with EDTA, thus etidronate inhibited ALP activity by chelation effects was concluded. We examined the effects of Zn, which is necessary for ALP activity, on ALP activity in P19 and RA-P19. Zn promoted ALP activity at a low concentration, but it inhibited ALP activity at a high concentration. It has been proposed that two types of Zn binding sites with either low- or high-affinity are present in P19 cells. Furthermore, our results suggested that changes in the low-affinity site of Zn with RA treatment caused differences in sensitivity of ALP activity to etidronate in P19 and RA-P19.[Conclusion] The changes in the Zn binding site, which are essential for inhibitory activity, changed sensitivity to the inhibitor along with ALP activity in tumor cells that lost organ-specific sensitivity to inhibitors.