ArticleBMC complementary and alternative medicine2013
Plant proteolytic enzyme papain abrogates angiogenic activation of human umbilical vein endothelial cells (HUVEC) in vitro.
Article in BMC complementary and alternative medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04742829 (Evaluation of the Effect of a Therapy With INTRAVIT® Tablets on Retinal Edema, Retinal Sensitivity and Visual Acuity in the Course of Diabetic Retinopathy), which is not on this map. Cited by 13 papers.
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Evaluation of the Effect of a Therapy With INTRAVIT® Tablets on Retinal Edema, Retinal Sensitivity and Visual Acuity in the Course of Diabetic Retinopathy
Who cites it
13 citing papers in PubMed, 37 citations in OpenAlex.
- Investigation of the effects of a Kiperin Bromelain & Papain complex in normal colon, mammary, and skin cells.Scientific reports · 2026Article
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- Green Nanotechnology Through Papain Nanoparticles: Preclinical in vitro and in vivo Evaluation of Imaging Triple-Negative Breast Tumors.Nanotechnology, science and applications · 2024Article
- Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.Cell death discovery · 2023Review
- Modulatory Effect of Papaya Extract against Chlorpyrifos-Induced Oxidative Stress, Immune Suppression, Endocrine Disruption, and DNA Damage in FemaleInternational journal of environmental research and public health · 2022Article
- Anti-Cancer Effects of α-Cubebenoate Derived fromMolecules (Basel, Switzerland) · 2022Article
- Nattokinase Attenuates Retinal Neovascularization Via Modulation of Nrf2/HO-1 and Glial Activation.Investigative ophthalmology & visual science · 2021Article
- Targeting the Stromal Pro-Tumoral Hyaluronan-CD44 Pathway in Pancreatic Cancer.International journal of molecular sciences · 2021Article
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- Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.Molecules (Basel, Switzerland) · 2020Review
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- The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis.Mediators of inflammation · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVascular endothelial growth factor (VEGF) is a key regulator of physiologic and pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. It is known that cysteine proteases from plants, like bromelain and papain are capable to suppress inflammatory activation. Recent studies have demonstrated that they may interfere with angiogenesis related pathways as well. The aim of this study was to investigate the anti-angiogenic effects of papain on human umbilical vein endothelial cells (HUVEC) in vitro.
methodsCell viability after prolonged treatment with papain was investigated by life cell staining and lactate dehydrogenase release assay. Angiogenic activation was assessed by ELISA against phosphorylated proteins AKT, MEK1/2, ERK1/2, SAPK/JNK and p38-MAPK. Growth inhibition was determined by means of an MTT-assay and cell migration by means of a scratch assay. Capability to form a capillary network was investigated using a tube formation assay.
resultsPapain did not induce proteolysis or cell detachment of HUVEC in a concentration range between 0 and 25 μg/mL. Four hours treatment with 10 μg/mL papain resulted in a reduced susceptibility of endothelial cells to activation by VEGF as determined by phosphorylation levels of Akt, MEK1/2, SAPK/JNK. Papain exerted a distinct inhibitory effect on cell growth, cell migration and tube formation with inhibition of tube formation detectable at concentrations as low as 1 μg/mL. Bromelain and ficin displayed similar effects with regard to cell growth and tube formation.
conclusionPapain showed a strong anti-angiogenic effect in VEGF activated HUVEC. This effect may be due to interference with AKT, MEK1/2 and SAPK/JNK phosphorylation. Two other plant derived cysteine proteases displayed similar inhibition of HUVEC cell growth and tube formation. These findings indicate that plant proteolytic enzymes may have potential as preventive and therapeutic agents against angiogenesis related human diseases.
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