College of Pharmacy, Guilin Medical University, Guangxi, Guilin, 541004, China.
Dalton Trans. 2023 Aug 22;52(33):11427-11440. doi: 10.1039/d3dt01648j.
A novel chiral oxazoline copper(II)-based complex {[Cu(CHNOS)]} (Cu-A) was synthesized by an reaction using L-methioninol, 4-hydroxyisophthalaldehyde, sodium hydroxide and copper(II) nitrate trihydrate as reactants. Its crystal structure was characterized. , Cu-A was superior to -dichlorodiammineplatinum (DDP) in cytotoxicity and angiogenesis inhibition. Cu-A significantly induced apoptosis of ovarian cancer cells (SKOV3) and human umbilical vein endothelial cells (HUVECs), showing significant anti-ovarian cancer and anti-angiogenesis effects. Notably, Cu-A significantly inhibits the growth of ovarian cancer in nude mice xenografted with SKOV3 cells, and it is less renal toxic than DDP. The molecular mechanism of anti-ovarian cancer and anti-angiogenesis is possibly that it down-regulates the expression of the proteins ERK1/2, AKT, FAK, and VEGFR2 and their phosphorylated proteins p-ERK1/2, p-AKT, p-FAK, and p-VEGFR2 in the VEGF/VEGFR2 signal transduction pathway to inhibit SKOV3 cell and HUVEC proliferation, induce apoptosis, suppress migration and metastasis, and inhibit angiogenesis. What's more, Cu-A significantly inhibits ovarian tumor growth by inhibiting tumor cells from inducing vascular endothelial cells to form their own vasculature and by inhibiting the expression of the anti-apoptotic protein Bcl-2 and up-regulating the expression of the pro-apoptotic proteins Caspase-9 and Bax to induce apoptosis of tumor cells.
一种新型的手性恶唑啉铜（II）配合物{[Cu（CHNOS）]}（Cu-A）是通过使用 L-甲硫氨酸醇、4-羟基异邻苯二醛、氢氧化钠和三水合硝酸铜作为反应物的反应合成的。其晶体结构得到了表征。与顺铂（DDP）相比，Cu-A 在细胞毒性和血管生成抑制方面具有优势。Cu-A 显著诱导卵巢癌细胞（SKOV3）和人脐静脉内皮细胞（HUVEC）凋亡，表现出显著的抗卵巢癌和抗血管生成作用。值得注意的是，Cu-A 显著抑制了 SKOV3 细胞荷瘤裸鼠的卵巢癌生长，其肾毒性低于 DDP。抗卵巢癌和抗血管生成的分子机制可能是通过下调 VEGF/VEGFR2 信号转导通路中 ERK1/2、AKT、FAK 和 VEGFR2 及其磷酸化蛋白 p-ERK1/2、p-AKT、p-FAK 和 p-VEGFR2 的表达，抑制 SKOV3 细胞和 HUVEC 的增殖，诱导细胞凋亡，抑制迁移和转移，并抑制血管生成。此外，Cu-A 通过抑制肿瘤细胞诱导血管内皮细胞形成自身血管，以及抑制抗凋亡蛋白 Bcl-2 的表达和上调促凋亡蛋白 Caspase-9 和 Bax 的表达，来显著抑制卵巢肿瘤的生长，从而诱导肿瘤细胞凋亡。
