Studies have not established the effect of papaya on breast cancer
Papayas (Carica papaya) and their seeds contain substances that have been shown to have antihypertensive, antioxidant, anti-amoebic, antiparasitic, antiseptic, wound and burn healing, contraceptive and neuroprotective properties, as well as improving cholesterol profile and assisting with digestion. Papaya is a good dietary source of vitamin C and vitamin A. The fruit has been selected to raise levels of vitamin A in children in deficiency-prone countries such as Cameroon and Sri Lanka. Compounds with known cancer-fighting properties found in papayas include carotenoids such as lycopene, beta-carotene and cryptoxanthin, as well as several isothiocyanates. The benzyl isothiocyanate found in papaya has been shown to induce apoptosis in pancreas, prostate, and leukemic cancer cells and to inhibit carcinogen-induced bladder cancer.Breast cancer-related effects of eating papaya
Benzyl isothiocyanate, found in papaya flesh and seeds, has been shown to selectively induce apoptosis in human breast cancer cells. The high carotenoid levels found in papayas suggest that consuming the fruit could serve to protect against breast cancer. However, no population studies have been performed that directly assess the effects of papaya on the risk of breast cancer.
Additional comments
Papayas are sometimes referred to as paw paws, but the paw paw (Asiminia triloba) sold in the U.S. is a different fruit. Papayas have two possible flesh colors, yellow and red. The red color of red papaya fruit is due to an accumulation of lycopene; the yellow color of yellow papaya is the result of conversion of lycopene to beta-carotene and beta-cryptoxanthin. Papayas should be eaten ripe, without the skin or seeds. Even though the peel is not eaten, papayas should be washed thoroughly before being cut up for consumption since potent pesticides typically are used in growing them.
Both raw and cooked green papayas (i.e., unripe papayas) are used in some Asian cuisines. For example, atchara, a Filipino condiment or side dish, is made of primarily of pickled raw green papaya. Ground papaya seeds are used in some cuisines similarly to black pepper. However, we recommend against consuming green papaya (whether raw, cooked or dried) or papaya seeds. Unlike ripe papaya, green papaya contains a high concentration of a type of latex that has been shown to produce uterine contractions in rats; this may be the basis for the belief in parts of Asia that consumption of papaya is unsafe during pregnancy. In fact, green papaya is used for female contraception and abortion in some traditional medicine systems.
Papaya seeds contain a higher proportion of benzyl isothiocyanate than does the flesh and they are sometimes used as part of herbal preparations. However, one study found that rats consuming papaya seed extract exhibited liver cell damage and precancerous liver changes in a dose-dependent manner. Papaya seed extracts also have been shown to have dose-dependent spermicidal effects, causing human sperm immobilization and death.
Dried papaya typically has been treated with sulfur dioxide to prevent the fruit from oxidizing during and after the drying process, thereby preserving its color. However, sulfur dioxide and its derivatives have been shown to increase the frequencies of chromosomal aberrations in mammalian cells and cause oxidative damage in multiple organs of male and female mice. Therefore, we recommend obtaining unsulfured dried fruit where possible.
Papain, a component of papaya found in some powdered meat tenderizers and some herbal supplements, has been shown to increase the effect of warfarin (coumadin) blood thinning therapy.
Selected studies
Screening of antiproliferative effect of aqueous extracts of plant foods consumed in Mexico on the breast cancer cell line MCF-7 International Journal of Food Sciences and Nutrition, May 2009In the present study, the antiproliferative effects of aqueous extracts of 14 plant foods commonly consumed in Mexico on MCF-7 breast cancer cells were evaluated. The foods studied included avocado, black sapote, guava, mango, prickly pear cactus stems (called nopal in Mexico) - both cooked and raw, papaya, pineapple, four varieties of prickly pear fruit, grapes and tomatoes. For each aqueous extract, beta-carotene, total phenolics and gallic acid contents, and antioxidant capacity were analyzed. Only the papaya extract was found to have a significant antiproliferative effect, as measured by a methylthiazolydiphenyl-tetrazolium bromide assay. There did not appear to be a direct relationship between the total phenolic content of a food and its antioxidant capacity with antiproliferative effect. The authors conclude that each plant food extract has its own unique combination of phytochemicals that determines its biological activity. In addition, papaya appears to be a very interesting candidate for further exploration of potential antineoplastic activities.
Longitudinal Biological Exposure to Carotenoids Is Associated with Breast Cancer–Free Survival in the Women's Healthy Eating and Living Study Cancer Epidemiology, Biomarkers & Prevention, February 2009
Some population studies have found a diet high in vegetables to be associated with less likelihood of recurrence in breast cancer survivors. Carotenoids, which are found primarily in vegetables and fruit, are thought to have biological activities that may specifically reduce the progression of breast cancer. The present study was designed to examine the relationship between plasma carotenoids at enrollment and at points in time one, two or three, four, and six years, and breast cancer-free survival. Cases were 3,043 participants in the Women's Healthy Eating and Living Study who had been diagnosed with early-stage breast cancer. The primary end point was time to either a second breast cancer recurrence or a new primary breast cancer. The analysis was adjusted for prognostic and other confounding factors. 508 (16.7%) breast cancer events (recurrence or new primary breast cancer) took place over a median 7.12 years of follow up. Compared with the lowest third, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83). The authors conclude that higher biological exposure to carotenoids was associated with greater likelihood of breast cancer–free survival when assessed over the time frame of the study.
Greater vegetable and fruit intake is associated with a lower risk of breast cancer among Chinese women International Journal of Cancer, February 2009
The present hospital-based case-control study was designed to examine the associations between fruit and vegetable consumption and risk of breast cancer. Four hundred and thirty-eight breast cancer cases in Guangdong, China were matched to 438 controls by age (5-year groupings) and location (rural/urban). Dietary factors were ascertained by interviews using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjusting for various potential confounders. Total overall fruit and vegetable consumption was found to be inversely associated with risk of breast cancer. The odds ratio of the highest fourth relative to the lowest quartile of total fruit consumption was 0.53 (95% CI 0.34-0.82) and for vegetable intake was 0.28 (95% CI 0.18-0.43). Consumption of banana, watermelon/papaya/cantaloupe, dark green leafy vegetables, cruciferous vegetables, carrots, and tomatoes were each significantly associated with lower breast cancer risk. An inverse association with breast cancer risk also was found for intakes of vitamin A, carotene, vitamin C, vitamin E, and fiber. The authors conclude that greater consumption of vegetables and fruits is associated with a lower risk of breast cancer among Chinese women residing in Guangdong.
Plasma Retinol and Prognosis of Postmenopausal Breast Cancer Patients Cancer Epidemiology, Biomarkers & Prevention, January 2009
The current prospective study was designed to assess the long-term prognostic role of retinol (vitamin A) plasma levels in postmenopausal breast cancer patients. Beta-carotene is broken down in the body to retinol. The cases were 208 postmenopausal women operated on for T1-2N0M0 early stage breast cancer who participated in a chemoprevention trial as controls and did not receive chemotherapy or hormone therapy. Blood samples were collected at a median of three months post surgery. Minimum and median follow-up were at 12 and 15 years, respectively (assuming survival). The main analyses were performed on all women and on also a subgroup aged 55 years (and assumed too far along in years to be in perimenopause). The main end point was death from breast cancer and the results were stratified for age (where relevant) and recruitment period, and adjusted for tumor size and histology. At the 12-year mark, patients with low levels of plasma retinol (< 2.08 µmol/L, median of distribution) were found to have lower rates of breast cancer survival than those with high retinol (log-rank P = 0.052); the difference was statistically significant for women 55 years (log-rank P = 0.006). The adjusted hazard ratios for low versus high levels of retinol were 2.11 (95% confidence interval, 1.08-4.14) for all women and 3.58 (95% confidence interval, 1.50-8.57) for those 55 years. The authors conclude that low plasma retinol strongly predicts poorer prognosis in postmenopausal breast cancer patients.
Molecular effects of fermented papaya preparation on oxidative damage, MAP Kinase activation and modulation of the benzo[a]pyrene mediated genotoxicity Biofactors, December 2008
In the present study, a fermented papaya (Carica papaya Linn) preparation was assessed for its ability to (1) modulate oxidative DNA damage due to hydrogen peroxide in rat PC12 pheochromocytoma (adrenal gland tumor) cells; and (2) protect the brains of hypertensive rats from oxidative damage. The involvement of oxidative and nitrosative stress mechanisms in processes such as aging, cancer, and cardiovascular and neurodegenerative diseases has continued to fuel suggestions that these processes can potentially be altered by treatment with free-radical scavengers and antioxidants. PC12 cells pre-treated with fermented papaya (50 g/ml) before incubation with hydrogen peroxide were found to have significantly increased viability and more sustained morphology and shape. Human HepG2 liver cancer cells exposed to hydrogen peroxide (50 M) exhibited an olive tail moment of 10.56 ± 1.44 compared with 1.37 ± 0.29 of the solvent control. A significant reduction (P 0.05) in DNA damage was seen at concentrations of 10 g/ml of fermented papaya. A level of 50 g/ml fermented papaya reduced the genotoxic effect of hydrogen peroxide by about 1.5-fold compared to hydrogen peroxide-only exposed cells. Similarly, concentrations of 50g/ml fermented papaya significantly reduced DNA migration in co-treated cells compared with only the carcinogen benzo[a]pyrene treated cells. A dose of 100g/ml fermented papaya was found to reduce the DNA damage two-fold. The ability of fermented papaya to regulate the phosphorylation status of ERK 1/2, Akt, and p38 was also evaluated. Fermented papaya demonstrated the potential to modulate hydrogen peroxide-induced ERK, Akt and p38 activation. The reduction of p38 phosphorylation induced by 250M hydrogen peroxide was found to be more pronounced. Supplementation with fermented papaya also significantly attenuated the increased decay rate constant of the MC-PROXYL (a blood brain barrier permeable nitroxyl spin probe) ESR signal in the hypertensive rat brain, suggesting modulation of oxidative stress. The authors conclude that fermented papaya can modulate oxidative injury, supporting the view that it could have a role in the prophylactic treatment of neurodegenerative diseases.
Dietary isothiocyanate mediated apoptosis of human cancer cells is associated with Bcl-xL phosphorylation International Journal of Oncology, October 2008
Benzylisothiocyanate (BITC), a major phase II enzyme inducer found in the organic solvent of papaya fruit, has previously been shown to trigger apoptosis specifically in cancer cells. In the current study, this dietary isothiocyanate was shown to induce significant apoptosis when pancreatic, prostate and leukemic cancer cells were exposed to it. The exogenous expression of dominant-negative caspase-8 or dominant-negative caspase-9 was found to reduce benzylisothiocyanate-mediated apoptosis of prostate cancer cells. In line with this observation, benzylisothiocyanate was found to activate both procaspase-8 and -9 in pancreatic and prostate cancer cells. The authors conclude that the molecular mechanism underlying the relationship between benzylisothiocyanate-mediated cell cycle arrest and apoptosis involves the anti-apoptotic protein Bcl-xL, which was phosphorylated by benzylisothiocyanate treatment. Jun kinase is also involved in benzylisothiocyanate triggered Bcl-xL phosphorylation and apoptosis.
Benzyl Isothiocyanate Targets Mitochondrial Respiratory Chain to Trigger Reactive Oxygen Species-dependent Apoptosis in Human Breast Cancer Cells Journal of Biological Chemistry, October 2008
The present study was designed to examine the mechanism by which benzyl isothiocyanate (BITC), a known dietary cancer chemopreventive agent, causes apoptosis in MDA-MB-231 and MCF-7 human breast cancer cells. Benzyl isothiocyanate-induced apoptosis in human breast cancer cells was found to be initiated by reactive oxygen species (ROS) due to inhibition of complex III of the mitochondrial respiratory chain. Treatment with benzyl isothiocyanate caused activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), which function upstream of Bax activation in apoptotic response to various activators. Pharmacological inhibition of both JNK and p38 MAPK conferred partial but significant protection against benzyl isothiocyanate-induced apoptosis. Normal human breast cells were found to be resistant to BITC-mediated ROS generation, JNK/p38 MAPK activation, and apoptosis. The authors conclude that benzyl isothiocyanate-induced apoptosis in human breast cancer cells is initiated by mitochondria-derived ROS.
Micellar oleic and eicosapentaenoic acid but not linoleic acid influences the β-carotene uptake and its cleavage into retinol in rats Molecular and Cellular Biochemistry, August 2006
The current study was designed to investigate the influence of oleic, linoleic and eicosapentaenoic acids on the bioavailability of β-carotene, including plasma β-carotene response and its conversion to retinol (vitamin A). The study was conducted by using single (9 hour time course) and repeated (10 days) dose administrations in rats. After a single dose, the levels of plasma β-carotene and retinyl palmitate in the oleic acid and eicosapentaenoic acid groups were higher by 13, 7 and 11, 6 folds than in the linoleic acid group (p < 0.05). The liver β-carotene level in the oleic acid and eicosapentaenoic acid groups were higher by 3 and 1.2 folds than in the linoleic acid group (p < 0.05). After 10 days' repeated dose, the plasma β-carotene and retinyl palmitate levels in oleic acid (6.2%, 51.7%) and eicosapentaenoic acid (25.4%, 17.23%) groups were higher than in the linoleic acid group (p < 0.05). The liver β-carotene level in oleic acid (21.2%) and eicosapentaenoic acid (17.6%) groups also were higher than in the linoleic acid group (p < 0.05). In both the experiments, the activity of β-carotene 15,15′-dioxygenase in the intestinal mucosa and plasma triglyceride levels were also found to be higher in the oleic acid and eicosapentaenoic acid groups than in the linoleic acid group. β-carotene excreted through the urine and feces of the oleic acid and eicosapentaenoic acid groups was lower than that of the linoleic acid group. The authors conclude that the results demonstrate an improved absorption and metabolism of β-carotene when fed a diet supplemented with oleic acid or eicosapentaenoic acid compared to linoleic acid.
Hepatotoxicity of the Methanol Extract of Carica papaya (Paw-Paw) Seeds in Wistar Rats Pharmaceutical Biology, June 2005
The present study examined the activity of Carica papaya Linn. seed extract in the liver of the Wistar albino rat. Tolerated doses of papaya were estimated in short-term toxicity studies. The doses were administered orally for 30 days, in single or repeated doses, to male adult rats. The rats were apportioned into 4 groups of 5 rats per group. Group one was given 10 mg/kg; group two was given 50 mg/kg; and group three was given 200 mg/kg. Group four, which was designated the control group, was given normal saline (1 ml/rat). All of the rats were sacrificed 24 hours after treatments were completed and blood samples were collected. A portion of each rat liver was also collected. Consumption of papaya seed extract was found to result in elevations of rat serum levels of acid phosphatase (ACP), alkaline phosphatase (ALP), and aspartate amino transferase (AST). Mild to severe metaplasia of hepatocytes in a dose-related manner, proliferation of Kupfer cells, and hepatic cells cirrhosis of the rat livers were also observed in rats receiving papaya seed extract. All of the observed biochemical and pathological effects indicated liver cell damage and malfunction. The authors conclude that seeds of Carica papaya should be used with care in herbal medicine to avoid toxicity.
Papaya (Carica papaya) consumption is unsafe in pregnancy: fact or fable? Scientific evaluation of a common belief in some parts of Asia using a rat model British Journal of Nutrition, August 2002
The current study was designed to assess the safety of papaya (Carica papaya) consumption during pregnancy, given that it is commonly avoided during pregnancy in some parts of Asia. Ripe papaya blend (500 ml/l water) was freely given to 4 groups of Sprague-Dawley rats at different stages of pregnancy (days 1-5, 6-11, 12-17 and 1-20). A control group of rats received water. The daily volumes of ripe papaya blend consumed by the treated groups were significantly higher than the water consumed by the controls. No significant differences were found between the rats given ripe papaya and the control group with respect to the number of implantation sites and viable fetuses and no signs of fetal or maternal toxicity was observed in any of the groups. The effects of ripe papaya juice and crude papaya latex on pregnant and non-pregnant rat uteri was also studied. Consumption of ripe papaya juice was found to have no significant contractile effect on uterine smooth muscles isolated from pregnant and non-pregnant rats. However, crude papaya latex (0.1-3.2 mg/ml) induced spasmodic contraction of the uterine muscles similar to oxytocin (1-64 mU/ml) and prostaglandin F(2 alpha) (0.028-1.81 microM). In the 18-19 day pregnant rat uterus, the effect of crude papaya latex was characterized by tetanic spasms. The authors conclude that normal consumption of ripe papaya during pregnancy may not pose any significant danger. However, unripe or semi-ripe papaya (which contain high concentration of the latex that produced the marked rat uterine contractions) could be unsafe during pregnancy.
