Possible Interaction: Tretinoin and Ubenimex

“The mechanism by which Bestatin enhances all-trans retinoic acid (ATRA)–induced cell differentiation of acute promyelocytic leukemia (APL) cells is generally attributed to inhibition of cell surface CD13/aminopeptidase N activity.”

“It is concluded that aminopeptidase N/CD13 inhibitor bestatin may enhance the differentiation-inducing activity of ATRA through inhibiting the phosphorylation of P38 MAPK in NB4 cells mediated by the cell surface APN/CD13.”

“100 microg/ml bestatin enhanced the NBT reduction activity in NB4 cells induced by various concentrations of ATRA (10, 20, 40 nmol/L).”

“From 48 to 96 hours, 100 microg/ml bestatin time-dependently increased NBT reduction in NB4 cells induced by 10 nmol/L ATRA (P < 0.01).”

“It is concluded that an aminopeptidase inhibitor bestatin can potentiate ATRA-inducing differentiation of NB4 cells, possibly by down-regulating c-myc expression in synergy with ATRA.”

“This study was purposed to investigate whether aminopeptidase inhibitor, bestatin , can potentiate all-trans retinoic acid (ATRA)-inducing differentiation in NB4 cells, and to explore its mechanism.”

“Various concentrations (50, … microg/ml) of bestatin combined with …/L ATRA down-regulated the expression of c-Myc protein, which was negatively correlated with the NBT reduction activity of NB4 … induced by 10 nmol/L ATRA alone or plus bestatin at various concentrations (r = -0.940, P = 0.017).”

“100 microg/ml of ubenimex could enhance the NBT reduction activity induced by 10 nmol/L of ATRA , intensify the down-regulation of c-Myc protein expression and inhibit the phosphorylation of p38MAPK protein induced by 10 nmol/L of ATRA in NB4 cells.”

“CONCLUSIONS Ub nimex co uld potentiate ATR A in duced differentiation in APL cells, which may be correlated with the inhibition of p38 MAPK protein phosphorylation and regulation of c-Myc protein expression.”

“ Bestatin synergistically enhanced the cytostatic effect of ATRA on NB4 cells.”

“We found that bestatin , an inhibitor of CD13/aminopeptidase N, enhanced the sensitivity of APL NB4 cells to ATRA at concentrations of 0.1-1000ng/ml.”