Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis

Pharm Biol. 2022 Dec;60(1):65-74. doi: 10.1080/13880209.2021.2013259.

Abstract

Context: Concanavalin A (Con A) exhibited multiple roles in cancer cells. However, the role of Con A in endothelial cells was not reported.

Objective: Our present study investigated the potential angiogenic role of Con A in endothelial cells and ischaemic hind-limb mice.

Materials and methods: Human umbilical vein endothelial cells and Ea.hy926 cells were employed to determine the effect of Con A (0.3, 1, and 3 μg/mL) or vehicle on angiogenesis and cell proliferation with tube formation, ELISA, flow cytometry, EdU, and western blot. Hind-limb ischaemic mice were conducted to determine the pro-angiogenic effect of Con A (10 mg/kg) for 7 days.

Results: Con A promoted tube formation to about three-fold higher than the control group and increased the secretion of VEGFa, PDGFaa, and bFGF in the medium. The cell viability was promoted to 1.3-fold by Con A 3 μg/mL, and cell cycle progression of G0G1 phase was decreased from 77% in the vehicle group to 70% in Con A 3 μg/mL, G2M was promoted from 15 to 19%, and S-phase was from 7 to 10%. Con A significantly stimulated phosphorylation of Akt and ERK1/2 and expression of cyclin D1 and decreased the expression of p27. These effects of Con A were antagonised by the PI3K inhibitor LY294002 (10 μM) and MEK pathway antagonist PD98059 (10 μM). Moreover, Con A (10 mg/kg) exhibited a repair effect in ischaemic hind-limb mice.

Discussion and conclusions: This study will provide a new option for treating ischaemic disease by local injection with Con A.

Keywords: Cell proliferation; HUVECs; PDGF; VEGF; bFGF; cell cycling.

MeSH terms

  • Angiogenesis Inducing Agents / administration & dosage
  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Chromones / pharmacology
  • Concanavalin A / administration & dosage
  • Concanavalin A / pharmacology*
  • Cyclin D1 / metabolism
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology
  • Hindlimb
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Ischemia / drug therapy
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / pharmacology
  • Neovascularization, Physiologic / drug effects*
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Chromones
  • Flavonoids
  • Morpholines
  • Concanavalin A
  • Cyclin D1
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Grants and funding

This study was supported by the National Natural Science Foundation of China [grant No. 81970283 and 81900336], a Joint Fund for Science and Technology Cooperation across the Taiwan Straits from the National Natural Science Foundation of China and Fujian Province [grant No. U1605226], a Science and Technology Project from Xiamen Science and Technology Bureau, Fujian Province, China [Grant No. 3502Z20184025 and 3502Z20184024], and a Youth Science Fund from Fujian Provincial Health and Family Planning Commission, Fujian Province, China [Grant No. 2017-2-109].