Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4’, 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dosedependent manner, with an estimated IC50 value of 54.4 μM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptormediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.

Quercetin is a natural flavonoid phytochemical that is extracted from various plants. Having an advantages due to its varied biological properties, such as anti-inflammatory, anti-viral, anti-oxidant, and anti-cancer effects, quercetin is used to treat many diseases. Recently, it has been reported that autophagy inhibition may play a key role in anti-cancer therapy. Therefore, in this study, we investigated the molecular mechanisms and anti-cancer effects of quercetin in human osteosarcoma cells via autophagy inhibition. We ascertained that quercetin inhibited cell proliferation and induced cell death, these process is demonstrated that apoptosis via the mitochondrial pathway and the caspase cascade. Quercetin also induced autophagy which was inhibited by 3-MA, autophagy inhibitor and the blockade of autophagy promoted the quercetin-induced apoptosis, confirming that autophagy is a pro-survival process. Thus, these findings demonstrate that quercetin is an effective anti-cancer agent, and the combination of quercetin and an autophagy inhibitor should enhance the effect of anti-cancer therapy.