A homogalacturonan from Lonicera japonica Thunb. disrupts angiogenesis via epidermal growth factor receptor and Delta-like 4 associated signaling

• Published in: Glycoconjugate journal Vol. 39; no. 6; pp. 725 - 735
• Main Authors: Liao, Wenfeng, Hu, Xiaodong, Du, Zhenyun, Wang, Peipei, Ding, Kan
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2022; Springer Nature B.V
• Subjects: Angiogenesis; Angiogenesis inhibitors; Antioxidants; Arthritis; Biochemistry; Biomedical and Life Sciences; Cancer therapies; Cell adhesion & migration; Cell migration; D-Galacturonic acid; Diabetes; Diabetic retinopathy; Epidermal growth factor; ErbB Receptors - analysis; Extracellular signal-regulated kinase; FDA approval; Flowers; Flowers - chemistry; Humans; Kinases; Laboratories; Life Sciences; Lonicera - chemistry; Lonicera japonica; MAP kinase; Metastasis; Microvasculature; Molecular weight; Notch1 protein; Original Article; Pathology; Phosphorylation; Polysaccharides; Polysaccharides - chemistry; Protein kinase; Proteins; Raf protein; Science; Signal Transduction; Tumors; Vascular endothelial growth factor; Angiogenesis; Dll4/Notch1 signaling; Homogalacturonan; EGFR/Raf/MEK/ERK signaling cascade; Lonicera japonica
• ISSN: 0282-0080; 1573-4986; 1573-4986
• DOI: 10.1007/s10719-022-10088-2

A homogeneous polysaccharide named as LJW2F2 was extracted and purified from the flowers of Lonicera japonica Thunb. Structural characteristic indicated that LJW2F2 was a homogalacturonan composed of α-1,4-D-galacturonic acid with a molecular weight of 7.2 kDa. Previous investigation suggested that homogalacturonan might impede angiogenesis, however the mechanism is still vague. Here we reported that LJW2F2 significantly disrupted capillary-like tube formation of human microvascular endothelia cells (HMEC-1) on matrigel as well as the cells migration. Mechanism study revealed that LJW2F2 might inactivate phosphorylation of epidermal growth factor receptor (EGFR), subsequently suppress Raf, mitogen-activated protein kinase (MEK) and extracellular-related kinase (ERK) phosphorylation. Moreover, LJW2F2 markedly decreased the expression of Notch1 and Delta-like ligand 4 (Dll4). Therefore, our results suggested that LJW2F2 might be a potential angiogenesis inhibitor via disturbing multiple signaling pathways. Graphical abstract