Acacetin and Pinostrobin Inhibit Malignant Breast Epithelial Cell Adhesion and Focal Adhesion Formation to Attenuate Cell Migration
Acacetin and Pinostrobin Inhibit Malignant Breast Epithelial Cell Adhesion and Focal Adhesion Formation to Attenuate Cell Migration
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DOI：
10.1177/1534735420918945
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发表时间：
2020-06-01
影响因子：
2.9
通讯作者：
Gehler, Scott
中科院分区：
文献类型：
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作者：
Jones, Aaron A.;Gehler, Scott
天然存在的类黄酮，如金合欢素和球松素，破坏肿瘤进展过程中的广泛过程，如细胞增殖，凋亡和血管生成。尽管已经使用各种细胞系研究了金合欢素和球松素的抗增殖和抗凋亡作用，但关于金合欢素和球松素对癌细胞迁移和转移的作用知之甚少。例如，目前还不清楚金合欢素或球松素是否对乳腺癌细胞迁移或粘附有任何影响。在这项研究中，我们评估了金合欢素和球松素对恶性MDA-MB-231和T47 D乳腺上皮细胞和非致瘤性MCF 10A乳腺上皮细胞的影响。我们的研究结果表明，金合欢素和球松素选择性抑制MDA-MB-231和T47 D细胞的迁移，以剂量依赖性的方式，同时表现出对MCF 10A细胞的钝化作用。有趣的是，这两种化合物对3种细胞系中的任何一种细胞增殖都没有影响。此外，金合欢素和球松素均抑制MDA-MB-231和T47 D细胞粘附、细胞铺展和粘着斑形成，但对MCF 10A细胞无显著影响。总的来说，这些结果表明，金合欢素和球松素选择性抑制恶性乳腺上皮细胞迁移，通过衰减细胞粘附和粘着斑形成。这些发现表明，金合欢素和球松素都可以作为潜在的治疗选择，以靶向乳腺肿瘤细胞迁移在晚期肿瘤进展。
Naturally occurring flavonoids, such as acacetin and pinostrobin, disrupt a wide range of processes during tumor progression, such as cell proliferation, apoptosis, and angiogenesis. Although the antiproliferative and antiapoptotic effects of acacetin and pinostrobin have been studied using various cell lines, relatively little is known about the effects of acacetin and pinostrobin on cancer cell migration and metastasis. For instance, it is unclear whether acacetin or pinostrobin have any effect on breast cancer cell migration or adhesion. In this study, we assessed the effects of acacetin and pinostrobin on malignant MDA-MB-231 and T47D breast epithelial cells and non-tumorigenic MCF10A breast epithelial cells. Our results demonstrate that both acacetin and pinostrobin selectively inhibit the migration of both MDA-MB-231 and T47D cells in a dose-dependent manner while exhibiting blunted effects on MCF10A cells. Interestingly, neither compound had an effect on cell proliferation in any of the 3 cell lines. Furthermore, both acacetin and pinostrobin inhibit MDA-MB-231 and T47D cell adhesion, cell spreading, and focal adhesion formation, but have no significant effect on MCF10A cells. Collectively, these results suggest that both acacetin and pinostrobin selectively inhibit malignant breast epithelial cell migration through attenuation of cell adhesion and focal adhesion formation. These findings indicate that both acacetin and pinostrobin may serve as potential therapeutic options to target breast tumor cell migration during late-stage tumor progression.