A novel chiral oxazoline copper(II)-based complex inhibits ovarian cancer growth in vitro and in vivo by regulating VEGF/VEGFR2 downstream signaling pathways and apoptosis factors

A novel chiral oxazoline copper(II)-based complex {[Cu(C H NO S) ]} (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 -dichlorodiammin...

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Published in:Dalton transactions : an international journal of inorganic chemistry 2023-08, Vol.52 (33), p.11427-11440
Main Authors: Fan, Rong, Wei, Jing-Chen, Xu, Bing-Bing, Jin, Nan, Gong, Xiao-Yi, Qin, Xiu-Ying
Format: Article
Language:English
Subjects:
Angiogenesis
Apoptosis
Biocompatibility
Cancer
Copper
Crystal structure
Endothelial cells
Ovarian cancer
Proteins
Signal transduction
Sodium hydroxide
Tumors
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Summary:A novel chiral oxazoline copper(II)-based complex {[Cu(C H NO S) ]} (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.
ISSN:1477-9226
1477-9234
DOI:10.1039/d3dt01648j