Dr. Weeks’ Comment: Cranberry fruit helps women with urinary tract infections but few people know how powerful and beneficial the cranberry is for men- especially men dealing with prostate issues. Here is some of the science supporting this remedy.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016 Dec;160(4):559-565
Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings
Vladimir Student 1 ,
Background and objectives:Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy.
Methods: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery.
Results: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine.
Conclusions: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.
Antioxidants (Basel). 2016 Aug 18;5(3):27. doi: 10.3390/antiox5030027.
Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents
Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.
J Cell Biochem. 2010 Oct 15;111(3):742-54. doi: 10.1002/jcb.22761.
Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways
Bob A Déziel 1 ,
Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individual’s diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti-cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25 µg/ml by 30% after 6 h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP-2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI-3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF-κB p65 protein to the nucleus. Cranberry PACs increased c-jun and decreased c-fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, NF-κB and AP-1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti-cancer agents.
Food Funct. 2012 May;3(5):556-64. doi: 10.1039/c2fo10145a. Epub 2012 Mar 5.
American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators
Bob Déziel 1 ,
Prostate cancer is one of the most common cancers in the world, and its prevalence is expected to increase appreciably in the coming decades. As such, more research is necessary to understand the etiology, progression and possible preventative measures to delay or to stop the development of this disease. Recently, there has been interest in examining the effects of whole extracts from commonly harvested crops on the behaviour and progression of cancer. Here, we describe the effects of whole cranberry extract (WCE) on the behaviour of DU145 human prostate cancer cells in vitro. Following treatment of DU145 human prostate cancer cells with 10, 25 and 50 μg ml⁻¹ of WCE, respectively for 6 h, WCE significantly decreased the cellular viability of DU145 cells. WCE also decreased the proportion of cells in the G2-M phase of the cell cycle and increased the proportion of cells in the G1 phase of the cell cycle following treatment of cells with 25 and 50 μg ml⁻¹ treatment of WCE for 6 h. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A, cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes in p16(INK4a) and pRBp107 protein expression levels also were evident, however, the changes noted in p16(INK4a) and pRBp107 protein expression levels were not statistically significant. These findings demonstrate that phytochemical extracts from the American cranberry (Vaccinium macrocarpon) can affect the behaviour of human prostate cancer cells in vitro and further support the potential health benefits associated with cranberries.
Res Rep Urol. 2017 Apr 26;9:65-69. doi: 10.2147/RRU.S133538. eCollection 2017.
Enteric-coated and highly standardized cranberry extract reduces antibiotic and nonsteroidal anti-inflammatory drug use for urinary tract infections during radiotherapy for prostate carcinoma
Introduction: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370®) in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was evaluated.
Methods: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489) or not (n=435) the enteric-coated, highly standardized cranberry extract for 6-7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann-Whitney Utest and Pearson’s χ2test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.
Results: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly standardized cranberry extract, while 107 of the 435 patients (24.6%) in the control group developed LUTIs (p=0.0001). A clear and significant reduction in urinary discomfort of ~50% was seen in treated subjects. The treatment also resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics.
Conclusion: The enteric-coated, highly standardized cranberry extract could be used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic therapy in patients receiving pelvic irradiation for prostate cancer.
Randomized Controlled Trial
Support Care Cancer. 2015 Jan;23(1):95-102. doi: 10.1007/s00520-014-2335-8. Epub 2014 Jul 4.
Standardized cranberry capsules for radiation cystitis in prostate cancer patients in New Zealand: a randomized double blinded, placebo controlled pilot study
Purpose: Acute radiation cystitis, inflammation of the bladder, is a common side effect in men receiving external beam radiation for prostate cancer. Although several treatments provide symptomatic relief, there is no effective treatment to prevent or treat radiation cystitis. Cranberry products have been associated with urinary tract health. This study aimed to determine the effect of highly standardized cranberry capsules (containing 72 mg proanthocyanidins [PACS]) compared with that of placebo capsules on the incidence and severity of radiation cystitis.
Methods: Forty-one men with prostate cancer participated in a double blinded randomized placebo controlled study. Men took one capsule a day at breakfast during treatment and for 2 weeks after treatment completion. Severity of urinary symptoms and the bother these caused were measured using the individual items of the urinary domain of the Modified Expanded Prostate Index Composite (EPIC).
Results: The incidence of cystitis was lower in men taking cranberry capsules (65%) compared with those that took placebo capsules (90%) (p = 0.058); severe cystitis was seen in 30% of men in the cranberry arm and 45% in the placebo arm (p = 0.30). Overall, the incidence of pain/burning was significantly lower in the cranberry cohort (p = 0.045). Men on the low hydration regimen who took cranberry had less pain/burning (p = 0.038), stronger urine steam (p = 0.030) and used significantly fewer pads/liners (p = 0.042), which was significantly different from those on the high hydration regimen (p = 0.028).
Conclusion: Men receiving radiation therapy for prostate cancer may benefit from using cranberry capsules, particularly those on low hydration regimens or with baseline urinary symptoms.
J Sci Food Agric. 2011 Mar 30;91(5):789-96. doi: 10.1002/jsfa.4330. Epub 2011 Feb 23.
Ursolic acid and its esters: occurrence in cranberries and other Vaccinium fruit and effects on matrix metalloproteinase activity in DU145 prostate tumor cells
Background: Ursolic acid and its cis- and trans-3-O-p-hydroxycinnamoyl esters have been identified as constituents of American cranberries (Vaccinium macrocarpon), which inhibit tumor cell proliferation. Since the compounds may contribute to berry anticancer properties, their content in cranberries, selected cranberry products, and three other Vaccinium species (V. oxycoccus, V. vitis-idaea and V. angustifolium) was determined by liquid chromatography-mass spectroscopy. The ability of these compounds to inhibit growth in a panel of tumor cell lines and inhibit matrix metalloproteinase (MMP) activity associated with tumor invasion and metastasis was determined in DU145 prostate tumor cells.
Results: The highest content of ursolic acid and esters was found in V. macrocarpon berries (0.460-1.090 g ursolic acid and 0.040-0.160 g each ester kg(-1) fresh weight). V. vitis-idaea and V. angustifolium contained ursolic acid (0.230-0.260 g kg(-1) ), but the esters were not detected. V. oxycoccus was lowest (0.129 g ursolic acid and esters per kg). Ursolic acid content was highest in cranberry products prepared from whole fruit. Ursolic acid and its esters inhibited tumor cell growth at micromolar concentrations, and inhibited MMP-2 and MMP-9 activity at concentrations below those previously reported for cranberry polyphenolics.
Phytother Res. 2009 Aug;23(8):1066-74. doi: 10.1002/ptr.2667.
Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin
Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells.
J Sci Food Agric. 2011 Oct;91(13):2303-7. doi: 10.1002/jsfa.4621. Epub 2011 Aug 30.
Cranberries: ripe for more cancer research?
Berries have been recognized as a functional food with potential to protect against a variety of health conditions, including some cancers. Cranberry (Vaccinium macrocarpon) production and consumption have grown in recent years, warranting further evaluation of potential health benefits. Extracts and isolated constituents from cranberry fruit inhibit growth and proliferation of tumor cells in vitro, and recent data from animal studies lend further support to cranberry’s reputation as a cancer fighter. Several likely mechanisms of action for cranberry against prostate and other cancers have been identified, including induction of apoptosis and inhibition of events linked to cellular invasion and migration. This article attempts to put into perspective what is known about cranberry’s potential chemopreventive properties, what is yet to be determined, and some factors to consider as research moves forward.
J Agric Food Chem. 2006 Dec 13;54(25):9329-39. doi: 10.1021/jf061750g.
Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro
Berry fruits are widely consumed in our diet and have attracted much attention due to their potential human health benefits. Berries contain a diverse range of phytochemicals with biological properties such as antioxidant, anticancer, anti-neurodegerative, and anti-inflammatory activities. In the current study, extracts of six popularly consumed berries–blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry–were evaluated for their phenolic constituents using high performance liquid chromatography with ultraviolet (HPLC-UV) and electrospray ionization mass spectrometry (LC-ESI-MS) detection. The major classes of berry phenolics were anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL. With increasing concentration of berry extract, increasing inhibition of cell proliferation in all of the cell lines were observed, with different degrees of potency between cell lines. The berry extracts were also evaluated for their ability to stimulate apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts showed the most significant pro-apoptotic effects against this cell line. The data provided by the current study and from other laboratories warrants further investigation into the chemopreventive and chemotherapeutic effects of berries using in vivo models.
Arch Ital Urol Androl. 2019 Oct 2;91(3). doi: 10.4081/aiua.2019.3.139.
Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer
During the last years, pharmaceutical innovations in primary care are dramatically less frequent and will be even more rare in the next future. In this context, preclinical and clinical research oriented their interest toward natural compounds efficacy and safety, supporting the development of a new “nutraceutical” science. Medicinal plants, in the form of plant parts or extracts of them, are commonly used for the treatment of prostate diseases such as benign hypertrophy, prostatitis and chronic pelvic pain syndrome. The pharmacological properties searched for the treatment of prostatic diseases are anti-androgenic, anti-estrogenic, antiproliferative, antioxidant and anti-inflammatory. The most studied and used medicinal plants are Serenoa repens, Pygeum africanum and Urtica dioica. Other promising plants are Cucurbita pepo, Epilobium spp, Lycopersum esculentum, Secale cereale, Roystonea regia, Vaccinium macrocarpon. In parallel, epidemiological studies demonstrated that diet may play an important role on incidence and development of prostatic diseases. The Mediterranean diet is rich of elements with anti-oxidant properties that act as a protective factor for prostatic cancer. Similarly, low intake of animal protein, high intake of fruits and vegetable, lycopene and zinc are a protective factor for benign prostatic hyperplasia (BPH). Serenoa repens in the treatment of symptoms of BPH has been tested either alone or, more frequently, in combination with other medicinal plants, alpha-blockers and inhibitors of 5- alpha reductase (5-ARI). Recent meta-analyses found the effectiveness of Serenoa repens similar or inferior of that of finasteride and tamsulosin but clearly higher than that of placebo in the treatment of mild and moderate low urinary tract symptoms (LUTS), nocturia and discomfort. Clinical trials showed potential synergistic effect of Serenoa repens with other medicinal plants and drugs. In addition to Serenoa repens, there are many other medicinal plants for which clinical evidence is still controversial. Urtica dioica, Pygeum africanum and Curcubita pepo can be considered as an adjunct to the common therapies and their use is supported by studies showing improvement of symptoms and flowmetric indices. Lycopene and selenium are natural products with antioxidant and anti-inflammatory action. The combination of lycopene and selenium with Serenoa repens was able to reduce inflammation in histological prostate sections and to further improve symptom scores and urinary flow in patients with BPH on tamsulosin treatment. Similar effects could be obtained with the use of other carotenoids, such as astaxanthin, and/or zinc. Efficacy on symptoms of patients with BPH of some polyphenols such as quercitin, equol and curcumin have been demonstrated by clinical studies. Pollen extract is a mixture of natural components able to inhibit several cytokines and prostaglandin and leukotriene synthesis resulting in a potent anti-inflammatory effect. Pollen extracts significantly improve symptoms, pain, and quality of life in patients affected by chronic pelvic pain syndrome and chronic prostatitis. Beta-sitosterol is a sterol able to improve urinary symptoms and flow measures, but not to reduce the size of the prostate gland. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide-signaling molecule with anti-inflammatory and neuroprotective effects that can have an interesting role in the management of chronic pelvic pain syndrome and chronic urological pain. Finally, several plant-based products have been subjected to preclinical, in vitro and in vivo, investigations for their potential pharmacological activity against prostate cancer. Some epidemiological studies or clinical trials evaluated the effects of beverages, extracts or food preparations on the risk of prostate cancer. Some plant species deserved more intense investigation, such as Camelia sinensis (green or black tea), Solanum lycopersicum (common tomato), Punica granatum (pomegranate), Glycine max (common soy) and Linum usitatissimum (linen).