Agathisflavone Enhances Retinoic Acid-Induced Neurogenesis and Its Receptors alpha and beta in Pluripotent Stem Cells

作者：Paulsen Bruna S; Souza Cleide S; Chicaybam Leonardo; Bonamino Martin Hernan; Bahia Marcus; Costa Silvia Lima; Borges Helena L; Rehen Stevens K^*

来源：Stem Cells and Development, 2011, 20(10): 1711-1721.

DOI：10.1089/scd.2010.0446

Flavonoids have key functions in the regulation of multiple cellular processes; however, their effects have been poorly examined in pluripotent stem cells. Here, we tested the hypothesis that neurogenesis induced by all-trans retinoic acid (RA) is enhanced by agathisflavone (FAB, Caesalpinia pyramidalis Tull). Mouse embryonic stem (mES) cells and induced pluripotent stem (miPS) cells growing as embryoid bodies (EBs) for 4 days were treated with FAB (60 mu M) and/or RA (2 mu M) for additional 4 days. FAB did not interfere with the EB mitotic rate of mES cells, as evidenced by similar percentages of mitotic figures labeled by phospho-histone H3 in control (3.4%+/- 0.4%) and FAB-treated groups (3.5%+/- 1.1%). Nevertheless, the biflavonoid reduced cell death in both control and RA-treated EBs from mES cells by almost 2-fold compared with untreated EBs. FAB was unable, by itself, to induce neuronal differentiation in EBs after 4 days of treatment. On the other hand, FAB enhanced neuronal differentiation induced by RA in both EBs of mES and miPS. FAB increased the percentage of nestin-labeled cells by 2.7-fold (mES) and 2.4 (miPS) and beta-tubulin III-positive cells by 2-fold (mES) and 2.7 (miPS) in comparison to RA-treated EBs only. FAB increased the expression of RA receptors alpha and beta in mES EBs, suggesting that the availability of RA receptors is limiting RA-induced neurogenesis in pluripotent stem cells. This is the first report to describe that naturally occurring biflavonoids regulate apoptosis and neuronal differentiation in pluripotent stem cells.

• 出版日期2011-10