Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and \u2013independent apoptosis via Smad or Akt signaling pathways in HOS cells

Cheng Huang,Jui-Chieh Chen,Yu-Hsuan Chen,Hsu-Feng Lu,Hsiu-Chen Huang,Wen-Hsiang Chou

doi:10.1186/s12906-020-2857-1

Abstract

BackgroundOsteosarcoma is the most common primary malignant bone tumor in children and adolescents and has also been associated with a high degree of malignancy and enhanced metastatic capacity. Curcumin (CUR) is well known for its anti-osteosarcoma activity. However, both demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown.MethodsTo evaluate the growth inhibitory effects of CUR, DMC and BDMC on osteosarcoma (HOS and U2OS), breast (MDA-MB-231), and melanoma (A2058) cancer cells, we employed the MTT assay, annexin V-FITC /7-AAD staining, and clonogenic assay.ResultsCUR,DMC, and BDMC all decreased the viability of HOS, U2OS, MDA-MB-231, and A2058 cancer cells. Additionally, CUR,DMC, and BDMC induced the apoptosis of HOS cells through activation of Smad 2/3 or repression of Akt signaling pathway. Furthermore, the combination of CUR,DMC, and BDMC synergistically reduced cell viability, colony formation and increased apoptosis than either two or a single agent in HOS cells.ConclusionsThe combination of these three compounds could be used as a novel target for the treatment of osteosarcoma.

Highlights

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has been associated with a high degree of malignancy and enhanced metastatic capacity
Cell viability assay The effect of CUR, DMC and BDMC on cell viability in U2OS, HOS, A2058, and MDA-MB-231 cells were examined by MTT assay
Treatment with 5–25 μM of CUR, DMC and BDMC for 24–48 h significantly resulted in inhibition of the HOS, U2OS, MDA-MB-231, and A2058 cell viability in a time- and concentration-dependent manner, but to varying extents (Fig. 2a and b)

Summary

Introduction

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and has been associated with a high degree of malignancy and enhanced metastatic capacity. Curcumin (CUR) is well known for its anti-osteosarcoma activity Both demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are natural curcumin analogues/congeners from turmeric whose role in osteosarcoma development remains unknown. Whether analogs of CUR, such as DMC and BDMC could regulate osteosarcoma cell proliferation to a similar extent as CUR and the mechanisms remain to be investigated. To our knowledge, this is the first time study to identify the anti-cancer effects of DMC and BDMC on osteosarcoma cells. We will investigate the effects of CUR, DMC and BDMC on cell proliferation in osteosarcoma (HOS and U2OS), breast (MDA-MB231), and melanoma (A2058) cancer cells in the present study

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