Pomegranate
Pomegranate
Pomegranate (Punica granatum) is an edible fruit originating in the Middle East. Pomegranate extracts have shown significant anti-tumour activity against human prostate cancer cells. A range of effects on various cancer cell lines, including breast, colon and prostate cells. Pomegranate juice, peel and oil have been shown to interfere with tumour cell proliferation, cell cycle, invasion and angiogenesis effects.
Clinical Summary
Source: Memorial Sloan Kettering Cancer Center
…Consumption of pomegranate juice was found to benefit patients with carotid artery stenosis, in those with hypertension, hyperlipidemia, mild to moderate erectile dysfunction, and in patients with coronary heart disease (CHD) , but had no effect in patients with chronic obstructive pulmonary disease (COPD) .
In a study of postmenopausal women, intake of pomegranate seed oil did not reduce hot flashes .
Pomegranate juice has been shown to suppress inflammatory cell signaling , inhibit prostate tumor growth and lower serum PSA levels, and also inhibit aromatase activity, endogenous estrogen biosynthesis and breast cancer cell proliferation in vitro.
Pomegranate (Punica granatum)
Source: CAM-CANCER (Extracts)
Pomegranate (Punica granatum) is an edible fruit originating in the Middle East, the juice of which is widely available commercially. Various parts of the fruit including the juice have been used traditionally to treat a range of ailments.
The juice and other extracts have shown a wide range of bioactivity in pre-clinical studies, such as anti-inflammatory, anti-infective and anti-oxidant effects.
On the basis of this research, beneficial effects are claimed in cancer, specifically in the prevention and treatment of prostate cancer.
Only two trials in human have been conducted to date: one an uncontrolled trial and the other a randomised controlled trial. Both were in patients with prostate cancer and both reported increased prostate specific antigen (PSA) doubling time.
Pomegranate juice has been widely consumed for many years and has been used in studies lasting up to 3 years and appears to be safe. A small number of cases of allergic reactions and possible interaction with warfarin have been reported. Limited safety data is available on extracts.
Mechanism(s) of action
In cancer prevention, the relevant activities include those on carcinogenesis, the cell cycle, differentiation and enzyme activity, including inhibition of carbonic anhydrase and aromatase. Activity relevant to treatment of cancer includes effects on angiogenesis, apoptosis, tumour cell invasion and proliferation. Pomegranate extracts have shown significant anti-tumour activity against human prostate cancer cells: cold-pressed oil and polyphenols extracted from the juice and pericarp (peel) suppressed the proliferation, pericarp polyphenols and seed oil inhibited growth of xenografts and various extracts suppressed invasion. Similar inhibition in tumour growth was shown in a subsequent animal study.
A significant decrease in serum prostate-specific antigen levels was also demonstrated. In breast cancer ellagitannin-derived compounds inhibited aromatase activity as well as cell proliferation. Ellagitannins also reduced inflammatory cell signalling in colon cancer while quercetin has been shown to inhibit lung cancer cell growth with effects via the cell cycle and induction of apoptosis. The juice appears to have great bioactivity than the single purified active ingredients.
Narrative reviews
A detailed review of the phytochemistry and pharmacological actions of all pomegranate components was published in 2007. The authors concluded that ‘the actions of Punica granatum components suggest a wide range of clinical applications for the treatment and prevention of cancer…’ However, this conclusion was based on the results of pre-clinical studies and only one clinical trial was mentioned. Subsequently, a review summarised the research relating to the effects of pomegranate in prevention of various cancers, including breast, colon, lung, prostate and skin cancers. Research showing inhibition of the growth of cancer cells in culture and in preclinical animal studies was described but, again, only one clinical trial was mentioned.
Clinical trials
Two clinical trials have been conducted, both in men with prostate cancer. The first was an open label, uncontrolled Phase II study. The aim was to assess the effects of pomegranate juice on prostate-specific antigen (PSA) in men with a rising PSA after surgery or radiotherapy. Men with a PSA between 0.2 and 5 ng/ml and a Gleason score of 7 or less were treated with 8 ounces of pomegranate juice daily until disease progression. Effect on serum PSA, serum-induced proliferation and apoptosis of prostate cancer cells, serum lipid peroxidation, and nitric oxide levels and safety, were all assessed. The 42 men recruited had a mean initial PSA of 1.05ng/ml and most had a Gleason score between 5 and 7. The treatment was well-tolerated with mean PSA doubling time decreasing from 15 months at baseline to 54 months post-treatment. Assays comparing the effects of pre-treatment and post-treatment patient serum on prostate cancer cell growth showed a 12% decrease in proliferation and a 17% increase in apoptosis, both statistically significant. The lack of a control group limits the conclusions that can be drawn from this trial but the fact that clinical effects were supported by in-vitro measures suggested further investigation of pomegranate was warranted.
The second study was a randomised, multi-centre Phase II trial, again in men with prostate cancer. This trial assessed the effect of two different doses of pomegranate extract on PSA doubling time. The patients recruited had a rising PSA, median age of 74.5 years with a median Gleason score of 7. They were treated for up to 18 months with either 1g or 3g pomegranate extract daily using capsules each containing 1g of polyphenol extract, equivalent to about 8 oz of pomegranate juice. The median PSA doubling time increased from 11.9 months at baseline to 18.5 months after treatment (P<0.001) but there was no significant difference between the effects of the two doses…
Pre-clinical studies
Pre-clinical studies have demonstrated a range of effects on various cancer cell lines, including breast, colon and prostate cells. Pomegranate juice, peel and oil have been shown to interfere with tumour cell proliferation, cell cycle, invasion and angiogenesis effects. Recent studies have also reported anti-oestrogenic effects 24 and a possible effect in sensitising cells to the cancer drug tamoxifen both potentially of benefit in breast cancer .
Citation
Karen Pilkington, CAM-Cancer Consortium. Pomegranate (Punica granatum) [online document]. http://www.cam-cancer.org January 16, 2013.
Document history
First published in January 2013, authored by Karen Pilkington.
References
- Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol. 2007 109(2):177-206.
- Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ, Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L, Belldegrun A. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006 12(13):4018-26.
- Paller CJ, Ye X, Wozniak PJ, Gillespie BK, Sieber PR, Greengold RH, Stockton BR, Hertzman BL, Efros MD, Roper RP, Liker HR, Carducci MA. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis. 2012 doi: 10.1038/pcan.2012.20.
- Albrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel A, Mansel RE, Neeman I, Geldof AA, Campbell MJ. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004 7(3):274-83.
- Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A. 2005 102(41):14813-8.
- Adams LS, Zhang Y, Seeram NP, Heber D, Chen S. Pomegranate ellagitannin-derived compounds exhibit antiproliferative and antiaromatase activity in breast cancer cells in vitro. Cancer Prev Res (Phila). 2010 3(1):108-13.
- Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 2005 16(6):360-7.
- Adhami VM, Khan N, Mukhtar H. Cancer chemoprevention by pomegranate: laboratory and clinical evidence. Nutr Cancer. 2009 61(6):811-5.
Published Clinical Trials / Studies / Reviews
Cancer chemoprevention by pomegranate: laboratory and clinical evidence.
Specific Pomegranate Juice Components as Potential Inhibitors of Prostate Cancer Metastasis
Updated 2024