Arsenic trioxide exerts a double effect on osteoblast growth in vitro

Abstract

Arsenic trioxide (ATO) is a promising antitumor agent used to treat acute promyelocytic leukemia (APL) and, recently solid tumor. The present study was designed to evaluate the effect of ATO proliferation of osteoblast that plays very important roles in maintaining the structure integrity and function of bone.Cell survives, apoptosis, collagen, and molecular targets were identified by multiple detecting techniques, including MTT assay, electron microscopy, collagen detecting kit, TUNEL kit, and western blot in hFOB1.19 human osteoblasts cell line. The results showed that low dose of ATO (0.25, 0.5, and 1μM) remarkably enhanced the viability of cultured osteoblasts in a concentration- and time-dependent manner. Intriguingly, a dual effect of high dose of ATO (5, 10, and 20μM) was also observed showing significant reduction in viability of culture osteoblasts at concentration- and time-dependent fashion. Moreover, low dose of ATO promoted secretion and synthesis of collagen, whereas high dose of ATO induced typical morphological characteristics of apoptosis in osteoblasts. Mechanically, western blot results demonstrated that low dose of ATO dramatically up-regulated TGF-β1 protein and activated p-AKT proliferative signaling. And, high dose of ATO increased Bax/Bcl-2 ratio in a time-dependent fashion and activated caspase-3 apoptotic signaling. These results demonstrate at the first time that ATO exerts a double effect on osteoblast function depending upon the concentration and provide a clue to rationally use ATO for clinicians to pay more attention to protect bone from the adverse effects of therapeutic dose of ATO during tumor therapy.