Abstract : Papain is a plant proteolytic enzyme for the cysteine proteinase family cysteine protease enzyme in which enormous progress has been made to understand its functions. Papain is found naturally in papaya (Carica papaya L.) manufactured from the latex of raw papaya fruits. The enzyme is able to break down organic molecules made of amino acids, known as polypeptides and thus plays a crucial role in diverse biological processes in physiological and pathological states, drug designs, industrial uses such as meat tenderizers and pharmaceutical preparations. The unique structure of papain gives it the functionality that helps elucidate how proteolytic enzymes work and also makes it valuable for a variety of purposes. In the present review, its biological importance, properties and structural features that are important to an understanding of their biological function are presented. Its potential for production and market opportunities are also discussed.
Conclusion : Papain has revealed to be an enzymatic protein of significant biological and economic importance. It is through the unique structure of papain that provides functionality and helps explain how this proteolytic enzyme works and also makes it valuable for a variety of purposes. Further researches on papain enzyme in understand the specificity, the structural the effect brought various thermodynamic pathways is of critical importance. Papain is found naturally in papaya which is a versatile plant having number of uses and enzymatic properties. Since the papaya grows in a wide range of climate, papaya production for extraction of papain can be a source of earning a high income to farmers.
Keyword :Proteolytic enzyme, cysteine protease, papain, structure, hydrophobic
Papaine - Enzyme of biological importance - A review - American Journal of Biochemistry and Biotechnology, 2012, 8 (2), 99-104 - ISSN: 1553-3468 - Ezekiel Amri and Florence Mamboya

Abstract : Papain, a phytotherapeutic agent, has been used in the treatment of eschars and as a debriding chemical agent to remove damaged or necrotic tissue of pressure ulcers and gangrene. Its benefits in these treatments are deemed effective, since more than 5000 patients, at the public university hospital at Rio de Janeiro, Brazil, have undergone papain treatment and presented satisfactory results. Despite its extensive use, there is little information about toxic and mutagenic properties of papain. This work evaluated the toxic and mutagenic potential of papain and its potential antioxidant activity against induced-H2O2 oxidative stress in Escherichia coli strains. Cytotoxicity assay, Growth inhibition test, WP2-Mutoxitest and Plasmid-DNA treatment, and agarose gel electrophoresis were used to investigate if papain would present any toxic or mutagenic potential as well as if papain would display antioxidant properties. Papain exhibited negative results for all tests. This agent presented an activity protecting cells against H2O2- induced mutagenesis.
Genotoxic and Cytotoxic Safety Evaluation of Papain (Carica papaya L.) Using In Vitro Assays Claudia R. da Silva, Marcia B. N. Oliveira, Ellen S.Motta, Gabriella S. de Almeida, Leandro L. Varanda, Marcelo de Padula, Alvaro C. Leitao, and Adriano Caldeira-de-Araujo, Journal of Biomedicine and Biotechnology Volume 2010, Article ID 197898, 8 pages

Background: Vascular 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 antiangiogenic effects of papain on human umbilical vein endothelial cells (HUVEC) in vitro.
Methods: Cell 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.
Results: Papain 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.
Conclusion: Papain 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. Keywords: Bromelain, Papain, Ficin, Angiogenesis, Endothelial cells, VEGF, Plant proteolytic enzymes
Plant proteolytic enzyme papain abrogates angiogenic activation of human umbilical vein endothelial cells (HUVEC) in vitro - Mohr and Desser BMC Complementary and Alternative Medicine 2013, 13:231 - Thomas Mohr and Lucia Desser.