Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding 071000, China.
Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University and Medical College of Hebei University, Baoding 071000, China.
Anticancer Agents Med Chem. 2019;19(10):1253-1261. doi: 10.2174/1871520619666190404155230.
Coumarins are a wide group of naturally occurring compounds which exhibit a wide range of biological properties such as anti-cancer activities. Here, we characterized the biological functions of three Triphenylethylene-Coumarin Hybrids (TCHs) both in cell culture and nude mouse model.
Cell proliferation assay was performed in the cell cultures of both EA.hy926 endothelial cell and breast cancer cell lines treated with different concentrations of compound TCH-10b, TCH-5a and TCH-5c. Flowcytometry assay and Western blotting were used to further investigate the effect and mechanism of TCH-5c on EA.hy926 cell proliferation and cell cycle. The effects of TCH-5c on endothelial cell migration and angiogenesis were determined using cytoskeleton staining, migration assay and tube formation assay. Inhibition of breast cancer cell line derived VEGF by TCH-5c was shown through ELISA and the use of conditioned media. SK-BR-3 xenograft mouse model was established to further study the anti-tumorigenic role of compound TCH-5c in vivo.
We found that compound TCH-5c has inhibitory effects on both vascular endothelial cells and breast cancer cell lines. Compound TCH-5c inhibited proliferation, resulted in cell death, increased p21 protein expression to induce G0/G1 arrest and changed endothelial cell cytoskeleton organization and migration in EA.hy926 endothelial cells. Compound TCH-5c also inhibited breast cancer cell line derived VEGF secretion, decreased breast cancer cell-induced endothelial cell tube formation in vitro and suppressed SK-BR-3 breast cancer cell-initiated tumor formation in vivo.
Our study demonstrates that the coumarin derivative TCH-5c exerts its anti-cancer effects by 1. inhibiting endothelial cell proliferation, migration. 2. suppressing tube formation and angiogenesis induced by breast cancer cells in vitro and in vivo. Our results have potential implications in developing new approaches against breast cancer.
香豆素是一组广泛存在的天然化合物，具有广泛的生物活性，如抗癌活性。在这里，我们在细胞培养和裸鼠模型中对三种三苯乙烯-香豆素杂合体（TCH）的生物学功能进行了表征。
用不同浓度的化合物 TCH-10b、TCH-5a 和 TCH-5c 处理 EA.hy926 内皮细胞和乳腺癌细胞系的细胞培养物，进行细胞增殖测定。流式细胞术和 Western blot 用于进一步研究 TCH-5c 对 EA.hy926 细胞增殖和细胞周期的影响和机制。用细胞骨架染色、迁移测定和管形成测定来确定 TCH-5c 对内皮细胞迁移和血管生成的影响。通过 ELISA 和使用条件培养基来显示 TCH-5c 对乳腺癌细胞系衍生的 VEGF 的抑制作用。建立 SK-BR-3 异种移植小鼠模型，以进一步研究化合物 TCH-5c 在体内的抗肿瘤作用。
我们发现化合物 TCH-5c 对血管内皮细胞和乳腺癌细胞系均有抑制作用。化合物 TCH-5c 抑制增殖，导致细胞死亡，增加 p21 蛋白表达诱导 G0/G1 期阻滞，并改变 EA.hy926 内皮细胞的细胞骨架组织和迁移。化合物 TCH-5c 还抑制乳腺癌细胞系衍生的 VEGF 分泌，减少乳腺癌细胞诱导的内皮细胞管形成体外，并抑制 SK-BR-3 乳腺癌细胞引发的肿瘤形成体内。
我们的研究表明，香豆素衍生物 TCH-5c 通过 1. 抑制内皮细胞增殖、迁移。2. 抑制乳腺癌细胞在体外和体内诱导的管形成和血管生成，发挥其抗癌作用。我们的结果为开发针对乳腺癌的新方法提供了潜在的意义。
