Lisiak Natalia, Paszel-Jaworska Anna, Totoń Ewa, Rubiś Błażej, Pakuła Martyna, Bednarczyk-Cwynar Barbara, Zaprutko Lucjusz, Rybczyńska Maria
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland.
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego Str, 60-355 Poznan, Poland.
Chem Biol Interact. 2017 Apr 25;268:136-147. doi: 10.1016/j.cbi.2017.03.008. Epub 2017 Mar 18.
This paper reports a study on the role of two synthetic derivatives of oleanolic acid (OA), HIMOXOL and Br-HIMOLID, in the regulation of cell migration and invasion and the underlying molecular mechanisms of breast cancer cells. The effect of the compounds on four breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-468, and T-47D) and also on noncancerous breast cells, MCF-12A, was reported. The compounds had no effect on the migration of MCF-12A cells. However, both the derivatives revealed a higher cytotoxicity than the maternal compound OA, and in sub-cytotoxic concentrations, they decreased the migration of MCF7, MDA-MB-231, and MDA-MB-468 breast cancer cells and also the invasion of MCF7 and MDA-MB-231 cells; although, the derivatives had no effect on the migration and invasion of T-47D cells. Both the derivatives of OA inhibited the cell migratory and invasive abilities of breast cancer cells by downregulating the expressions of ITGB1, PTK2, and PXN genes and by decreasing the phosphorylation status and the level of its respective proteins (integrin β1, FAK, and paxillin, respectively). This study is the first to report the antimigratory and anti-invasive activities of HIMOXOL and Br-HIMOLID in breast cancer cells.
本文报道了一项关于齐墩果酸（OA）的两种合成衍生物HIMOXOL和Br-HIMOLID在调节乳腺癌细胞迁移和侵袭中的作用及其潜在分子机制的研究。报道了这些化合物对四种乳腺癌细胞系（MCF7、MDA-MB-231、MDA-MB-468和T-47D）以及非癌性乳腺细胞MCF-12A的影响。这些化合物对MCF-12A细胞的迁移没有影响。然而，这两种衍生物均显示出比母体化合物OA更高的细胞毒性，并且在亚细胞毒性浓度下，它们降低了MCF7、MDA-MB-231和MDA-MB-468乳腺癌细胞的迁移以及MCF7和MDA-MB-231细胞的侵袭；尽管如此，这些衍生物对T-47D细胞的迁移和侵袭没有影响。OA的这两种衍生物均通过下调ITGB1、PTK2和PXN基因的表达，并降低其各自蛋白质（分别为整合素β1、FAK和桩蛋白）的磷酸化状态和水平，来抑制乳腺癌细胞的迁移和侵袭能力。本研究首次报道了HIMOXOL和Br-HIMOLID在乳腺癌细胞中的抗迁移和抗侵袭活性。
