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.

中文翻译：

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姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素通过 Smad 或 Akt 信号通路在 HOS 细胞中诱导半胱天冬酶依赖性和非依赖性细胞凋亡。

背景骨肉瘤是儿童和青少年中最常见的原发性恶性骨肿瘤，并且还与高度恶性和增强的转移能力有关。姜黄素 (CUR) 以其抗骨肉瘤活性而闻名。然而，去甲氧基姜黄素 (DMC) 和双去甲氧基姜黄素 (BDMC) 都是来自姜黄的天然姜黄素类似物/同源物，其在骨肉瘤发展中的作用仍然未知。方法 为了评估 CUR、DMC 和 BDMC 对骨肉瘤（HOS 和 U2OS）、乳腺（MDA-MB-231）和黑色素瘤（A2058）癌细胞的生长抑制作用，我们采用 MTT 法，膜联蛋白 V-FITC /7 -AAD 染色和克隆形成测定。结果 CUR、DMC 和 BDMC 均降低了 HOS、U2OS、MDA-MB-231 和 A2058 癌细胞的活力。此外，CUR、DMC、BDMC通过激活Smad 2/3或抑制Akt信号通路诱导HOS细胞凋亡。此外，在 HOS 细胞中，CUR、DMC 和 BDMC 的组合协同降低了细胞活力、集落形成和增加了细胞凋亡。结论 这三种化合物的组合可作为治疗骨肉瘤的新靶点。