Antitumor effect of curcumin analog on osteosarcoma through the inhibition of p300‑mediated histone acetylation.

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Histone acetyltransferases (HATs), such as p300, CBP and PCAF, modulate numerous biological processes, including cellular proliferation and oncogenesis, through histone acetylation. In the present study, it was investigated whether the curcumin analogs such as pentagamavunon‑1 (PGV‑1) and chemoprevention curcumin analog‑1.1 (CCA‑1.1) could target p300 and suppress OS. Computational analysis indicated that PGV‑1 and CCA‑1.1 bind to the HAT domain of p300. Accordingly, these analogs efficiently inhibited the HAT activity of p300 in vitro and promoted OS cell apoptosis, accompanied by downregulation of acetylated histone H3 at Lys‑27 and phosphorylated oncogenic STAT3 at Tyr‑705. Finally, it was found that PGV‑1 and CCA‑1.1 but not PGV‑1, significantly attenuates the growth of OS developed on the chicken egg chorioallantoic membrane (CAM). Collectively, the present results strongly suggest that curcumin analog‑mediated targeting of p300 might provide a clue to develop an effective treatment strategy against patients with OS.