Papain in Papaya Leaf has Potential for Tumors; Breast Cancer

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The Scottish Doctor John Beard discovered that by injecting the proteases taken from a young calf into a cancerous human tumor his patients could be cured.

Research in Brazil on the protease papain (can be taken from the raw papaya fruit or the leaves of the papaya tree) shows a potential contemporary use of papain on implant surgery to prevent painful fibrous buildup.

This is similar action to Dr Beard’s thinking centuries ago to inject a cancerous, fibrous tumor with a protein dissolving enzyme. It seems this action may also have systemic effect via the bloodstream, as Dr Nam Dang proved similar effect on tumors as well from the action of papaya leaf tea.

See the Brazilian study from 2008:

INTERNATIONAL JOURNAL OF BIOLOGY AND BIOMEDICAL ENGINEERING

“The capsular contracture is the most common adverse effect after breast implant [1]. Fibrotic tissue promotes compression around the implant which distorts and deforms the mass which then compromises the aesthetic result and is associated with painful symptoms [2]-[4]. The development of a fibrotic capsule around foreign material is a physiologic reaction of the organism to protect itself from material it does not recognize [5]. The severity of capsule contracture is directly related to the degree of the local inflammatory reaction [6] and does not depend on the implant surface employed [7]. Although it is not clear the pathogenesis of capsular contracture, this phenomenon seems to be multifactorial [8].
Currently, there is no effective preventive measure for capsule contracture [8]. The conventional treatment may be surgical, by capsulectomy (or capsulotomy) or implant replacement and pharmacological using steroids, anti- leukotrienes, anti-TGF-β, antibiotics or antiinflamatories [2], [3].
Up to now there has been no accurate and reproducible pathologic model for examining capsular contracture [9]. This study assumes that eventual interference by papain (PA) on normal healing could be useful in further studies of a more complex model with induced capsule contracture [9].
Some authors have speculated on the possible modulator action of certain proteolytic enzymes present around the implants in the early stages of healing [10], [11].
Papain is a thiol endopeptidase plant whose activity is similar to the lysosomal cathepsin B enzyme with fibrinolytic and proteolytic action on the normal healing mechanism [12].
It has been suggested that the papain could be helpful when used locally around the implant at the surgical procedure, promoting tissue repair with less fibrotic tissue, thus avoiding the capsule contracture.
The aim of this study was to investigate the papain effects on the fibrous capsule thickness, collagen fibers density and myofibroblasts around textured implants in rats.
Abstract— Objective: To study the tissue repair around the textured mammary implants under the action of papain (PA). Conclusion: The papain drug decreased the fibrous capsule formation around the textured silicon implants in rats.”

The papain local depot impairs the capsule fibrous healing around textured silicone implants in rats.
Marcio Moreira, Djalma José Fagundes, Sanderland José Tavares Gurgel

http://www.naun.org/main/NAUN/bio/19-152.pdf

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In with the Old (Protease Therapy for Cancer); On with the NEW (Papain in Papaya Leaf as the Protease)

Proponent of Protease Enzyme Therapy for Cancer, Dr. Gonzales, carefully reviewed prior clinical studies performed by Dr. Kelley at Cornell University and the treatments were shown to have effect.
“Historically, large doses of proteolytic enzymes, along with diet, nutritional supplements, and “detoxification” procedures, have been used in alternative therapies to treat all forms of cancer, without formal clinical studies to support their use. A 2-year, unblinded, 1-treatment arm, 10-patient, pilot prospective case study was used to assess survival in patients suffering inoperable stage II-IV pancreatic adenocarcinoma treated with large doses of orally ingested pancreatic enzymes, nutritional supplements, “detoxification” procedures, and an organic diet. From January 1993 to April 1996 in the authors’ private practice, 10 patients with inoperable, biopsy-proven pancreatic adenocarcinoma were entered into the trial. After one patient dropped out, an 11th patient was added to the study (however, all 11 are considered in the data tabulation). Patients followed the treatment at home, under the supervision of the authors. As of 12 January 1999, of 11 patients entered into the study, 9 (81%) survived one year, 5 (45%) survived two years, and at this time, 4 have survived three years. Two patients are alive and doing well: one at three years and the other at four years. These results are far above the 25% survival at one year and 10% survival at two years for all stages of pancreatic adenocarcinoma reported in the National Cancer Data Base from 1995. This pilot study suggests that an aggressive nutritional therapy with large doses of pancreatic enzymes led to significantly increased survival over what would normally be expected for patients with inoperable pancreatic 6|Page adenocarcinoma.”

-“Evaluation of Pancreatic Proteolytic Enzyme Treatment of Adenocarcinoma of the Pancreas, With Nutrition and Detoxification Support”
Nicholas Gonzales and Linda Lee Isaacs
Nutrition and Cancer, volume 33 -Issue 2 March 1999 , pages 117 – 124

Protease Enzymes for Cancer Doctor/ Scientists 2005 and prior:

Beard, Dr. John
Howell, Dr. Edward
Wolf, Dr. Max
Benitez, Helen
Ranzberger, Dr. Karl
Kelley, Dr. William Donald
Gonzales, Dr. Nicholas
Isaacs, Dr. Linda
Good, Dr. Robert
Nieper, Dr. Hans
Murray, Dr.
Trnka, Dr. Frantisek
Novak, Dr. Josef F.

Papain in the Papaya Leaf May Drive Cancer Cell Attack

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.

http://www.hindawi.com/journals/bmri/2010/197898/

Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 197898, 8 pages
http://dx.doi.org/10.1155/2010/197898
Research Article
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.
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- 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.
1. Introduction
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 [1].
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 [10].
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 [13].
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 [15]. 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 [15].
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 [16]. 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 [16]. 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 [12].
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 [18].
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 [28].
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.

Researching Papaya Leaf Tea: The Julia Ruffin Project

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The Julia Ruffin Project researches, grows, and promotes papaya leaf tea.

The project is looking for microfarming partners all over the world to hand-grow and harvest the tea in a method that produces the finest taste and quality. If a microfarm can produce organic papaya leaf product that meets the project standard then the project may participate to package and brand with the project name, country of origin, and farmer.

The Julia Ruffin Project promotes only scientific and clinical studies and ethno medicine on or related to the potential medicinal value of papaya leaf tea.

See http://www.papayaleavesforcancer.com for more project details.

パパイヤは、がんのために葉, पपीता कैंसर के लिए पत्तियां, มะละกอใบสำหรับโรคมะเร็ง, Daun betik untuk Kanser, di papaia per il cancro, Листья папайи для Рака, Feuilles de papaye pour le cancer, Folhas de papaia para o cancro, Παπάγια Φύλλα για τον καρκίνο, Julia Ruffin Project, Papai Majani ya Saratani ya, Papaya blare vir Kanker Foglie, Papaya Blätter für Krebs, Papaya Dahon para sa Cancer, Papaya Hojas para el cáncer, Papaya Kanser bırakır, papaya leaves for cancer, Papaya levelek a rák, Pepaya Daun untuk Kanker, پاپایا برگ برای سرطان, 木瓜葉癌症,

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Antibody Structure of the Enzyme in Papaya Leaf

Diagram from Life Technologies Site:
http://www.lifetechnologies.com/us/en/home/references/molecular-probes-the-handbook/technical-notes-and-product-highlights/antibody-structure-and-classification.html

The Life Technologies diagram is referring to the antibody structure of papain. Papain is one of two unique primary enzymes found in the papaya leaf. Notice the binding to macrophages… These can be thought of as the "trash collection" at the cellular level.

This company is a major player in the Pharma industry and takes room to make note of the special antibody binding of papain.

In an earlier blog on this site a study is reviewed that tested papaya leaf and its potential as an antibiotic for six potent human diseases.

The Julia Ruffin Project researches, grows and promotes papaya leaf tea.

See http://www.papayaleavesforcancer.com

For ITP Drink Papaya Leaf Tea

“ITP, Idiopathic thrombocytopenic purpura is a bleeding disorder in which the immune system destroys platelets, which are necessary for normal blood clotting. Persons with the disease have too few platelets in the blood.

ITP is sometimes called immune thrombocytopenic purpura.”
-from MedlinePlus

The International Council on Infectious Diseases published a trial on Dengue patients (a similar platelet disorder) and tested with 5ml of papaya leaf extract per day on the subjects.

http://www.xcdsystem.com/icid2012/58.016.html

This amount of 5ml (less than a tablespoon) did not seem to have a significant effect on patients in this study. Ironically, the ethno medicine practiced around the world requires significantly more papaya leaf tea or extract per day and multiple times per day.

The study below finds papaya leaf effective against low platelet counts:

“Dengue virus, the main cause of dengue fever induces bone marrow suppression. Since bone marrow is the manufacturing center of blood cells, its suppression causes deficiency of blood cells leading to low platelet count. Anaemia and spontaneous severe bleeding are the other consequences of bone marrow suppression. Dengue virus can bind to human platelets in presence of virus specific antibody and cause immune mediated clearance of platelets[7]. Spontaneous aggregation of platelets to vascular endothelial cell pre-infected by virus induces aggregation, lysis and platelet destruction. Anti-platelet antibodies
generated after dengue virus infection causes destruction of platelets. Moreover, dengue virus causes platelet reduction and vascular alteration which is the principal factor causing haemorrhagic problems[8].
Vinca-alkaloids have been proven effective against anti-platelet macrophages in patients suffering from Idiopathic Thrombocytopenic Purpura (ITP)[9]. The saponins in Panax notoginseng have been shown to reduce platlet adhesion and aggregation, prevent thrombosis and improve microcirculation[7]. Carica papaya leaves contain various phytoconstituents like saponins, tannins, cardiac glycosides and alkaloids.

The alkaloids present include carpaine, pseudocarpaine and dehydrocarpaine I and II. These constituents can act on the bone marrow, prevent its destruction and enhance its ability to produce platelets. Moreover, it can also prevent platelet destruction in the blood and thereby increase the life of the platelet in circulation.”

The Journal of Pharmacognosy and Phytochemistry
Vol. 1 No. 5 2013 http://www.phytojournal.com Page | 59
http://phytojournal.com/vol1Issue5/Issue_jan_2013/11.1.pdf