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Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and -independent apoptosis via Smad

Cheng Huang^1,2, Hsu-Feng Lu^3,4, Yu-Hsuan Chen⁵

¹Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.

BMC Complementary Medicine and Therapies

|March 5, 2020

Abstract

Background:

Osteosarcoma 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.

Methods:

To 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.

Results:

CUR,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.

Conclusions:

The combination of these three compounds could be used as a novel target for the treatment of osteosarcoma.

Keywords:

Apoptosis Bisdemethoxycurcumin Curcumin Demethoxycurcumin Osteosarcoma

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