Memorial Sloan Cancer Center Records that Papaya Leaf Has Anti- Tumor Effect

“Papaya leaves exhibit anti-tumor, immunomodulatory (1), and antioxidant(9) effects in vitro….

Mechanism of Action
Papaya leaf extract modulates the immune system by enhancing the production of Th1 type cytokines, such as interleukin (IL-12), interferon (IFN-gamma) and tumor necrosis factor (TNF-alpha). Fractions with molecular weight less of than 1000 are most active in inhibiting tumor cell growth.”

The record on the website cites the references below:
1. Otsuki N, Dang NH, Kumagai E, et al. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J Ethnopharmacol. Feb 17 2010;127(3):760-767.
9. Okoko T, Ere D. Reduction of hydrogen peroxide-induced erythrocyte damage by Carica papaya leaf extract.Asian Pac J Trop Biomed.2012 Jun;2(6):449-53.”

Constituents Recorded in the papaya leaf:
Carpaine, malic acid, quinic acid, manghaslin and clitorin, minor quantities of various malic acid derivatives, nicotiflorin, and rutin.(6)
Phenolic compounds: Dimethoxycoumarin, protocatechuic acid, p-coumaric acid, caffeic acid, chlorogenic acid, kaempferol and quercetin. (8)”

Research 38 years ago: Papain Digests Liver Cancer Cells

Papain is one of the active cancer-fighting enzymes in the papaya leaf.

In 1976 the non-profit group, the Regina Elena Institute for Cancer Research sponsored a study on the effect of papain on the external wall of the liver cancer tumor cell. These malignant tumor cells show odd social behavior and unusual growth patterns. The cells on the external wall of the tumor were shown to be affected by papain in a way to slow growth. As quoted below from the study, Papain digests (gets rid of) the Navikaff (liver cancer) cells.

“…Papain digestion of Navikaff cells released cell surface gly capeptides that contained approximately 27% of the neura minidase-labile sialic acid…”

Effect of Neuraminidase and Papain Treatment on Lectin induced Agglutination of Novikoff Tumor Cells and Assay of Lectin Receptor Activity of the Glycopeptides Released from the Cell Surface by Papain

1Giovanni Neil
2 M. Christina Giuliano, Sylvia Capetillo, Ellen B. Gilliam, Douglas C. Hixson
3 and Earl F. Walborg, Jr.
4 Regina Elena Institute for Cancer Research,Viale Regina Elena N. 291, Rome,Italy [G. N., M. C. G.]; Department of Biochemistry.the University of Texas System Cancer Center,
M. D. Anderson Hospital and Tumor Institute [S. C., E. B. G., E. F. W.J;
and the University of Texas Health Science Center at Houston, Graduate School of Biomedical Sciences [D. C. H.], Houston,Texas77025

Papain in Papaya Leaf has Potential for Tumors; Breast Cancer


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:


“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

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.

Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 197898, 8 pages
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.
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.

Long Island Iced Papaya Leaf Tea

A new recipe for Long Island Papaya Leaf Tea may be as healthy as it is relaxing!

Substitute papaya wine for sweet & sour. According to some Nigerian study in 2012, papaya wine was healing to rats liver in a study compared to red wine, which in same quantity caused rat liver failure. This substitute may actually save some damage to your liver from four other white liquors… And it tastes great!


Details on the study are found in the book on papaya wine at: