Effects of the retinoic receptor agonists on proliferation of myelocytic leukemia cells

Abstract

All-trans retinoic acid (ATRA) is used to treat some of acute myelocytic leukemia (AML) such as acute promyelocytic leukemia (APL). Since ATRA shows biological activities binding to its receptor retinoic acid receptor (RAR), we compared anti-proliferative activity against AML cell line HL-60 cells between ATRA as pan-RAR agonist and tamibarotene and Am580 as RAR alpha agonist. We investigated effects of tamibarotene and Am580 synthesized as retinoic acid receptor agonists compared with ATRA. HL-60 cells were incubated with ATRA, tamibarotene and Am580 for several days. Cell number was counted and total RNA was extracted from the cells after the incubation. Quantitative RT-PCR was performed to quantify the mRNA levels of cyclin A2, cyclinD1, c-myc, CD11b, and glyceraldehyde-3-phospahte dehydrogenase as internal control.

Tamibarotene and Am580 showed an anti-proliferative activity in HL-60 cells. The effects of those compounds were weaker than ATRA when compared at the same concentration. Tamibarotene suppressed cyclin A mRNA level as well as c-myc mRNA in a time-dependent manner. Tamibarotene strikingly augmented CD11b levels as much as ATRA. These results suggest that tamibarotene has similar effects as ATRA in terms of anti-proliferative effects and induction of CD11b. Tamibarotene is suggested to have additional effects on signaling related to cell cycle.