Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and -independent apoptosis via Smad or Akt signaling pathways in HOS cells
Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and -independent apoptosis via Smad or Akt signaling pathways in HOS cells
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DOI：
10.1186/s12906-020-2857-1
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发表时间：
2020-03-03
影响因子：
3.9
通讯作者：
Huang, Hsiu-Chen
中科院分区：
文献类型：
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作者：
Huang, Cheng;Lu, Hsu-Feng;Huang, Hsiu-Chen
背景：骨肉瘤是儿童和青少年最常见的原发性恶性骨肿瘤，且恶性程度高、转移能力增强。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/同系物，其在骨肉瘤发展中的作用仍不清楚。 方法：为了评估 CUR、DMC 和 BDMC 对骨肉瘤（HOS 和 U2OS）、乳腺癌（MDA-MB-231）和黑色素瘤（A2058）癌细胞的生长抑制作用，我们采用MTT测定、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HOS、U2OS、MDA-MB-231和A2058癌细胞的活力。此外，CUR、DMC和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，与两种药物或单一药物相比，CUR、DMC 和 BDMC 的组合可协同降低 HOS 细胞中的细胞活力、集落形成并增加细胞凋亡。结论：这三种化合物的组合可用作治疗骨肉瘤的新靶点。
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.