A Novel Bromomelatonin Derivative Suppresses Apoptosis with Regulating the Expression of Bcl-2 Family Genes

Yoshikazu      Mikami; Masanori      Somei; Eri      Watanabe; Nobukazu      Watanabe; Tomihisa      Takahashi; Masaki      J. Honda

Abstract

SSH-BM-I is a new synthetic compound that is synthesized from Bromomelatonin by using a newly developed synthetic method. Recently, our group demonstrated that SST-VED-I-1, which has a similar chemical structure to SSHBM- I, inhibits starvation-induced apoptosis in osteoblasts. However, the effects of SSH-BM-I on apoptosis in osteoblasts have not yet been examined. Therefore, this study examined the effects of this compound on apoptosis in osteoblasts. In the present study, MC3T3-E1 mouse osteoblasts were used and apoptosis was induced by ultraviolet radiation (UV). We investigated the effect of SSH-BM-I on apoptosis by analyzing Caspase3/7 activity, translocation of Phosphatidylserine (PS), and mRNA expression levels of Bcl-2 and Bax. We found that SSH-BM-I suppressed UV-induced cell death in a dose-dependent manner, which was accompanied with the inhibition of Caspase activation and translocation of PS. Furthermore, SSH-BM-I up-regulated Bcl-2 expression and down-regulated Bax expression. These results suggest that SSH-BM-I has an inhibitory effect on apoptosis in osteoblasts through a Bcl-2 family-dependent signaling pathway.

Keywords: SSH-BM-I, Bromomelatonin, Tryptamine, Apoptosis, Bcl-2, Bax, Bax expressio, Phosphatidylserine (PS), ultraviolet radiation (UV), Rollinia mucosa, breast cancer cells, osteoblastic activity, hemocytometer, trypsinized