Tamibarotene

Tamibarotene slightly inhibits the growth of both myeloma cells and HUVECs, and remarkably inhibits the growth of HUVECs stimulated by VEGF. Tamibarotene shows little growth inhibition of bone marrow stromal cells (BMSCs), but it markedly inhibits migration of HUVECs by cocultured myeloma cells. Tamibarotene inhibits VEGF-induced phosphorylation of VEGF receptor. Tamibarotene significantly inhibits VEGF-induced formation of tube-like structures in vitro and neovascularization in mouse corneas. ^[1] Tamibarotene-induced HL-60 cell adhesion to ECs is 38% lower than All-trans retinoic acid (ATRA), and NB4 cell adhesion to ECs by tamibarotene is equivalent to ATRA, which induces CD38 gene transcription biphasically in HL-60 cells, the early-phase induction via DR-RARE containing intron 1, and the delayed-phase induction via RARE lacking the 5'-flanking region. Tamibarotene induces only the early-phase induction in HL-60 cells, resulting in its lower CD38 induction than ATRA. ^[2] Tamibarotene has negligible growth inhibition of peripheral blood mononuclear cells but marked growth inhibition of both HTLV-I-infected T-cell lines and ATL cells. Tamibarotene arrests cells in the G1 phase of the cell cycle and induces apoptosis in HTLV-I-infected T-cell lines. Tamibarotene inhibits also the phosphorylation of IkappaBalpha and NF-kappaB-DNA binding, in conjunction with reduction of expression of proteins involved in the G1/S cell cycle transition and apoptosis. Tamibarotene also inhibits the expression of JunD, resulting in suppression of AP-1-DNA binding. ^[3]

Tamibarotene treatment reduces significantly the insoluble Abeta levels in brain of mice, in particular Abeta(42), while it gives no apparent effects on the soluble Abeta levels. ^[4]