Traditionally the enzyme papain, a protease unique to papaya, has been harvested from the unripe fruit. The leaves are also packed with papain, but in a more consumable state as tea.
Enzyme scientists Beard and Howell showed the effect of proteases (like papain) on cancer and other disease. Theoretically the protein-dissolving enzyme papain eats the protein coating around the cancer cell.
The Brazilian research below on papain, cancer, ecoli and toxicity below is of interest.
Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 197898, 8 pages
Genotoxic and Cytotoxic Safety Evaluation of Papain (Carica papaya L.) Using In Vitro Assays
Claudia R. da Silva,1,2,3,4 Marcia B. N. Oliveira,1,2 Ellen S. Motta,2 Gabriella S. de Almeida,1,3 Leandro L. Varanda,1,3 Marcelo de Pádula,3,4 Alvaro C. Leitão,3 and Adriano Caldeira-de-Araújo1,2
1Laboratório de Análise de Toxicidade em Fitoterápicos, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, UERJ, 20551-030 Rio de Janeiro, RJ, Brazil
2Laboratório de Radio e Fotobiologia, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, UERJ, 20551-030 Rio de Janeiro, RJ, Brazil
3Laboratório de Radiobiologia Molecular, Instituto de Biofísica Carlos Chagas Filho, UFRJ, 21941-902 Rio de Janeiro, RJ, Brazil
4Laboratório de Diagnóstico Molecular e Hematologia, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, UFRJ, 21941-902 Rio de Janeiro, RJ, Brazil
Received 23 November 2009; Revised 16 March 2010; Accepted 16 March 2010
Academic Editor: Michael Cunningham
Copyright © 2010 Claudia R. da Silva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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- 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 -induced mutagenesis.
The belief that natural medicines are much safer than synthetic drugs has caused exceptional growth in human exposure to natural products, as plants, phytotherapeutic agents, and phytopharmaceutical products. This fact has lead to a resurgence of scientific interest in their biological effects. In most countries there is no universal regulatory system insuring the safety and activity of natural products and they had not been sufficiently investigated analytically or toxicologically .
Herbal medicines can be potentially toxic to human health. In this way, scientific research has shown that many plants used in traditional and folk medicine are potentially toxic, mutagenic, and carcinogenic [1–9].
Carica papaya L. (C. papaya L.) is the most important species within the Caricaceae genus, being widely cultivated for consumption as a fresh fruit, as juices, and as dried and crystallized fruit. Papaya also has several industrial uses [10–12]. Biochemically, its leaves and fruits are complex, representing sources of several proteins and alkaloids with important pharmaceutical, medical, and industrial applications. The juice is used for curing warts, cancer, and tumors. Leaves have been poultice into nervous pain. The hypoglycemic effect has been reported. It is used to treatment of infected wounds, malignant tumors, and burns .
The juice of ripe papaya displayed in vivo and in vitro activities against oxidative stress [13, 14]. It is an efficient scavenger of highly reactive hydroxyl radicals () formed during 60Co irradiation .
The green (unripe) papaya, which is rich in papain, is used for dressing of ulcers. This treatment is described as effective and it is recommended in preference to other dressings for chronic skin ulcers. It has been used in many countries such as England, Nigeria, Ghana, Gambia, India, and Jamaica . In spite of its extensive use, the following disadvantages were described, as problems concerning the availability of green papaya and difficulties in preparing and storing papaya .
The demonstration of the phytotherapeutic potential of a given species is a difficult task, since plant extracts consist of complex mixtures of major compounds, minor concomitant agents, and fibers, which can all be involved in the observed effects. Thus, given the difficulties in determining the contribution of a specific substance in the biological effects exerted by whole extracts, the aim of this work was the study of papain isolated from C. papaya, which possesses vast application in medicine.
Papain, a purified protein extracted from the latex of the unripe papaya, is widely used by Brazilian nurses in traditional medicine. It can be an alternative to green papaya and it can be used as phytotherapeutic agent in the treatment of pressure ulcers, gangrene, eschars, and as a debriding chemical agent to remove damaged or necrotic tissue . Papain is sometimes used in association with hydrous magnesium silicate (talc). Its benefits in these treatments are deemed effective, since more than 5000 patients at the Pedro Ernesto 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, mutagenic, and antioxidant properties of papain itself or even unripe papaya, which contains high concentration of papain .
Short-term tests have been used to check compounds for their ability to induce lesions in DNA, which may lead to genotoxicity, cytotoxicity, or mutagenicity. The experimental techniques using microbial cells such as Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), as well as assays using DNA as the target molecule, allowed the development of new tools to investigate toxic and mutagenic potentials of many physical and chemical agents and their correlation with the effects in eukaryotic systems [1, 17–20].
Hydrogen peroxide (H2O2) is a normal cell metabolite formed in several enzymatic and nonenzymatic reactions. H2O2 leads to oxidative stress, mutagenicity, loss of cell function, and ultimately apoptosis or necrosis [18, 21, 22]. In E. coli, a major component of the H2O2 toxicity is attributed to DNA damage mediated by the Fenton reaction, which generates reactive oxygen species (ROSs), such as [21–27]. E. coli possesses a number of antioxidant enzymes and DNA repair activities encoded by several genes (xthA, mutY, oxyR, among others) to counteract DNA damage caused by oxidative stress. Mutant strains lacking one or more of those genes are usually hypersensitive to H2O2 [18, 21, 22, 26]. So, Blanco and coworkers (1998) designed a series of E. coli WP2 tester strains (IC203 up to IC207, used in this study), which are useful for the screening of mutations resulting from oxidative stress as well in studies on antioxidants .
It is well documented that oxidative damage has been implicated in various systemic chronic diseases such as cancer, Alzheimer’s disease, rheumatoid arthritis, cardiovascular disease, cataracts, and other ageing processes. Reactive oxygen species (ROSs) are essential intermediates in oxidative metabolism. Nonetheless, when generated in excess, ROSs in various active forms can damage tissues .
In recent years, there has been a considerable interest in finding natural antioxidants from plant materials to replace synthetic molecules. Data from both scientific reports and laboratory studies show that plants contain a large variety of substances that possess antioxidant activity. Phytochemicals with antioxidant effects include some cinnamic acids, coumarins, diterpenes, flavonoids, lignans, monoterpenes, phenylpropanoids, tannins, and triterpenes. Natural antioxidants occur in all higher plants and in all parts of the plant (wood, bark, stems, pods, leaves, fruit, roots, flowers, pollen, and seeds) [29, 30].
The present work was carried out to evaluate the potential cytotoxic and mutagenic effects of papain using E. coli strains and plasmid DNA. In addition, we have also investigated papain antioxidant and antimutagenic activities against oxidative stress induced by H2O2.