Free Shipping on All Orders $75 Or More!

Your Trusted Brand for Over 35 Years

Life Extension Magazine

<< Back to June 2018

Pomegranate Thwarts Cancer on Multiple Levels

June 2018

By Gene Richmond

For years, scientists have been intrigued by pomegranate’s potential anti-cancer benefits.

Researchers are now discovering bioactive compounds in pomegranate can help thwart cancer at multiple stages of the development process.1-3

Pomegranate compounds are demonstrating the ability to protect against initial DNA mutations and impede existing cancers from spreading.1-7

All parts of the pomegranate plant, including the fruit, peel, and seeds, are rich in compounds that protect against chemical and physical threats to our cells.

These compounds include several families of polyphenols called tannins and flavonoids.1,3-5,8,9

What you need to know

  • Pomegranate extracts contain large amounts of a wide range of polyphenols known to have cancer-preventive properties.
  • Studies now show that pomegranate has tremendous potential to act as a powerful chemopreventive agent against prostate, breast, colorectal, and lung cancers through a series of overlapping, complementary mechanisms.
  • These mechanisms include protecting DNA from damage, inhibiting excessive cell growth, promoting natural cancer-cell death by apoptosis, and preventing cancer from spreading.
  • Regular pomegranate extract supplementation, one of nature’s greatest sources of bioactive polyphenols, may help protect the body from succumbing to cancer-causing processes.

Pomegranate’s Multiple Anti-Cancer Actions

Pomegranate extracts help combat cancer in several of the stages of tumor development.

Firstly, they interfere with multiple factors that damage DNA and cause the crucial first mutations of genetic material.1,10,11

If a mutation does occur, pomegranate extracts can:

  • Impede the cell replication cycle.1,7,12-14
  • Facilitate the death of mutated cells by apoptosis.6,9,12,15-17
  • Impede new blood-vessel growth, or angiogenesis. This helps starve rapidly dividing tumors of nutrients and oxygen.9,18-20

If a malignant cell mass still manages to develop, pomegranate extracts impair its ability to invade local tissues and metastasize to distant ones.12,15,21

A Potent Cancer Blocker

Pomegranate extracts also have the unique ability to promote the production of a protective enzyme known as paraoxonase-1, or PON-1.8,22-30

PON-1 blocks the inflammation and oxidative stress that can contribute to the initial DNA damage that can trigger cancer.31-41

People with cancer have been found in multiple studies to have reduced levels of PON-1, while those with the poorer prognosis often have the lowest levels of PON-1 activity.31-41

Restoring and promoting PON-1 activity may be a powerful means of blocking cancer formation at its earliest stages—while reducing oxidative stress and inflammation can be beneficial at multiple stages.

As we’ll see next, these anti-cancer actions play a role in pomegranate’s ability to help prevent four of the most common—and deadliest—cancers: prostate, breast, colorectal, and lung.

Pomegranate Slows Prostate Cancer Growth

IMAGE TAG  

Prostate cancer is the second leading cause of cancer-related death in American men.42 Both animal and human studies have shown pomegranate’s ability to slow prostate tumor growth and prevent prostate cancers from forming.

Animal studies have found that pomegranate extracts slow prostate tumor growth in the lab and in mice prone to prostate cancer.16,19,42-46 The extracts work by inhibiting cell proliferation (inducing apoptosis), reducing inflammation, and inhibiting new blood-vessel formation—many of the anti-cancer mechanisms mentioned above.9,16,19,42,45

In the most dramatic of these studies, 100% of mice bred to be prone to prostate cancer developed tumors by 20 weeks, compared to only 20%-30% of those receiving pomegranate fruit extract.43 More importantly, the supplemented mice lived as much as 114% longer than the control animals.

Human studies have also shown pomegranate’s ability to slow prostate cancer growth, as demonstrated by PSA scores.

Prostate-specific antigen (PSA) is a reliable marker of the rate of prostate cancer growth. The PSA doubling time is the standard indicator of tumor growth rate. The shorter the doubling time, the more aggressive the tumor.

Among men with rising PSA, pomegranate supplementation lengthened the PSA doubling time by 1.6- to 3.6-fold.47,48

This represents increases of 6 to 39 months in the time it took the PSA to double, a respectable slowing of tumor growth by any standard.47,48

Protection Against Breast Cancer

IMAGE TAG  

Breast cancer is the most common cancer among all women.49 It strikes nearly a quarter of a million women each year, killing more than 41,000.49

Most breast cancers are hormone-dependent, meaning that high levels of estrogen help the cancer to grow and spread.

Anti-estrogen therapies are a common form of treatment. They work by either lowering estrogen levels or by stopping estrogen from stimulating cancer growth.

A smaller percentage of breast cancers are hormone-independent, making them harder to treat using anti-estrogen therapies.

Pomegranate extracts have shown preventive activity in laboratory studies against estrogen-dependent breast cancer cells,6,50,51 with a pair of related human cancer cell studies finding that pomegranate peel and seed extracts inhibited the growth of breast cancer cells by more than 80%.52,53

Pomegranate has the unique ability to interact with the body’s normal hormone metabolism, making it especially beneficial against the more common hormone-dependent breast cancers.

Compounds found in pomegranates can inhibit the enzymes that convert less active forms of estrogen into cancer-promoting estrogen molecules.54

These results show pomegranate can block specific pathways that link estrogen metabolism to breast cancer.

Early Promise in Colorectal Cancer Prevention

Colorectal cancers are the third leading cause of cancer-related deaths in the U.S., accounting for more than 50,000 fatalities each year.55

Colon cells are constantly exposed to the flow of waste matter, toxins, and other materials capable of imposing powerful oxidative stress on cells. This makes them prime candidates for DNA damage, inflammation, and other factors that contribute to cancer.

The good news about colorectal cancers is that these tumors are also directly exposed to beneficial nutrients that we ingest.

Pomegranate extract is one of the best candidates for colorectal cancer chemoprevention because its polyphenols are delivered directly to human colonic tissues after consumption.56

In animal models of colorectal cancer, pomegranate extracts consistently—and significantly—inhibited tumor growth, reducing both the size and number of tumors.57,58 Pomegranate’s anti-cancer mechanisms included upregulating cellular anti-cancer enzyme systems.57,58

One of pomegranate’s most abundant classes of polyphenols, punicalagins, can inhibit enzymes capable of converting pro-carcinogens (precursors of cancer-causing molecules) into active carcinogens.59

Promising human studies have shown important alterations in genes and other markers of colorectal cancers when people supplement with pomegranate extracts.56,60,61

Lung Cancer

IMAGE TAG  

Pomegranate extracts have demonstrated properties against lung cancers.

In particular, pomegranate extracts have anti-inflammatory properties. This is valuable in reducing cancer risk because of the tumor-promoting effects of chronic inflammation.14,20

In animal models of lung cancer, pomegranate extracts reduced the numbers of tumors10,20 by as much as 66% compared with unsupplemented animals.20 These beneficial effects are attributed to slowing cell-replication and amplifying cell death by apoptosis.4,6,9,12,52

Finally, pomegranate extracts reduce production of specialized enzymes that cancer cells use to invade healthy cells.12 This property can help prevent cancer cells from spreading to other tissues, which lowers the deadliness of any cancer.

Summary

IMAGE TAG  

Pomegranate extracts have numerous properties capable of combatting cancer at multiple stages of the development process.

Studies show that pomegranate extracts protect DNA from mutations that trigger the earliest carcinogenic changes, inhibit cancer-cell growth, and help prevent cancer from spreading.

Pomegranate extracts show promise in preventing the growth and spread of four common types of cancer cells: prostate, breast, colon, and lung.

Their broad range of anti-cancer activities, attributable to their rich polyphenol content, makes them an excellent food and/or extract to ingest on a regular basis.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Bassiri-Jahromi S. Punica granatum (Pomegranate) activity in health promotion and cancer prevention. Oncol Rev. 2018;12(1):345.
  2. Faria A, Calhau C. The bioactivity of pomegranate: impact on health and disease. Crit Rev Food Sci Nutr. 2011;51(7):626-34.
  3. Syed DN, Chamcheu JC, Adhami VM, et al. Pomegranate extracts and cancer prevention: molecular and cellular activities. Anticancer Agents Med Chem. 2013;13(8):1149-61.
  4. Adhami VM, Khan N, Mukhtar H. Cancer chemoprevention by pomegranate: laboratory and clinical evidence. Nutr Cancer. 2009;61(6):811-5.
  5. Panth N, Manandhar B, Paudel KR. Anticancer Activity of Punica granatum (Pomegranate): A Review. Phytother Res. 2017;31(4):568-78.
  6. Sharma P, McClees SF, Afaq F. Pomegranate for Prevention and Treatment of Cancer: An Update. Molecules. 2017;22(1).
  7. Turrini E, Ferruzzi L, Fimognari C. Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy. Oxid Med Cell Longev. 2015;2015:938475.
  8. Shiner M, Fuhrman B, Aviram M. Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic anti-oxidants via PPAR gamma and AP-1 pathway activation. Atherosclerosis. 2007;195(2):313-21.
  9. Adaramoye O, Erguen B, Nitzsche B, et al. Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells. Chem Biol Interact. 2017;274:100-6.
  10. Husari A, Hashem Y, Zaatari G, et al. Pomegranate Juice Prevents the Formation of Lung Nodules Secondary to Chronic Cigarette Smoke Exposure in an Animal Model. Oxid Med Cell Longev. 2017;2017:6063201.
  11. Paller CJ, Pantuck A, Carducci MA. A review of pomegranate in prostate cancer. Prostate Cancer Prostatic Dis. 2017;20(3):265-70.
  12. Li Y, Yang F, Zheng W, et al. Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro. Biomed Pharmacother. 2016;80:227-35.
  13. Dai Z, Nair V, Khan M, et al. Pomegranate extract inhibits the proliferation and viability of MMTV-Wnt-1 mouse mammary cancer stem cells in vitro. Oncol Rep. 2010;24(4):1087-91.
  14. Khan N, Hadi N, Afaq F, et al. Pomegranate fruit extract inhibits prosurvival pathways in human A549 lung carcinoma cells and tumor growth in athymic nude mice. Carcinogenesis. 2007;28(1):163-73.
  15. Deng Y, Li Y, Yang F, et al. The extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells. Biomed Pharmacother. 2017;93:976-84.
  16. Naiki-Ito A, Chewonarin T, Tang M, et al. Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis. Prostate. 2015;75(2):151-60.
  17. Dikmen M, Ozturk N, Ozturk Y. The antioxidant potency of Punica granatum L. Fruit peel reduces cell proliferation and induces apoptosis on breast cancer. J Med Food. 2011;14(12):1638-46.
  18. Lee ST, Wu YL, Chien LH, et al. Proteomic exploration of the impacts of pomegranate fruit juice on the global gene expression of prostate cancer cell. Proteomics. 2012;12(21):3251-62.
  19. Sartippour MR, Seeram NP, Rao JY, et al. Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo. Int J Oncol. 2008;32(2):475-80.
  20. Khan N, Afaq F, Kweon MH, et al. Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice. Cancer Res. 2007;67(7):3475-82.
  21. Liu H, Zeng Z, Wang S, et al. Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9. Cancer Biol Ther. 2017;18(12):990-9.
  22. Estrada-Luna D, Martinez-Hinojosa E, Cancino-Diaz JC, et al. Daily supplementation with fresh pomegranate juice increases paraoxonase 1 expression and activity in mice fed a high-fat diet. Eur J Nutr. 2018;57(1):383-9.
  23. Khateeb J, Gantman A, Kreitenberg AJ, et al. Paraoxonase 1 (PON1) expression in hepatocytes is upregulated by pomegranate polyphenols: a role for PPAR-gamma pathway. Atherosclerosis. 2010;208(1):119-25.
  24. Lou-Bonafonte JM, Gabas-Rivera C, Navarro MA, et al. The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases. Int J Mol Sci. 2017;18(2).
  25. Parsaeyan N, Mozaffari-Khosravi H, Mozayan MR. Effect of pomegranate juice on paraoxonase enzyme activity in patients with type 2 diabetes. J Diabetes Metab Disord. 2012;11(1):11.
  26. Rock W, Rosenblat M, Miller-Lotan R, et al. Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities. J Agric Food Chem. 2008;56(18):8704-13.
  27. Rosenblat M, Volkova N, Aviram M. Pomegranate juice (PJ) consumption antioxidative properties on mouse macrophages, but not PJ beneficial effects on macrophage cholesterol and triglyceride metabolism, are mediated via PJ-induced stimulation of macrophage PON2. Atherosclerosis. 2010;212(1):86-92.
  28. Rosenblat M, Volkova N, Borochov-Neori H, et al. Anti-atherogenic properties of date vs. pomegranate polyphenols: the benefits of the combination. Food Funct. 2015;6(5):1496-509.
  29. Sohrab G, Ebrahimof S, Sotoudeh G, et al. Effects of pomegranate juice consumption on oxidative stress in patients with type 2 diabetes: a single-blind, randomized clinical trial. Int J Food Sci Nutr. 2017;68(2):249-55.
  30. Wu PT, Fitschen PJ, Kistler BM, et al. Effects of Pomegranate Extract Supplementation on Cardiovascular Risk Factors and Physical Function in Hemodialysis Patients. J Med Food. 2015;18(9):941-9.
  31. Ahmed NS, Shafik NM, Elraheem OA, et al. Association of paraoxonase-1(Q192R and L55M) gene polymorphisms and activity with colorectal cancer and effect of surgical intervention. Asian Pac J Cancer Prev. 2015;16(2):803-9.
  32. Arenas M, Garcia-Heredia A, Cabre N, et al. Effect of radiotherapy on activity and concentration of serum paraoxonase-1 in breast cancer patients. PLoS One. 2017;12(11):e0188633.
  33. Atay AE, Kaplan MA, Evliyaoglu O, et al. The predictive role of Paraoxonase 1 (PON1) activity on survival in patients with metastatic and nonmetastatic gastric cancer. Clin Ter. 2014;165(1):e1-5.
  34. Bobin-Dubigeon C, Jaffre I, Joalland MP, et al. Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence. Clin Biochem. 2012;45(16-17):1503-5.
  35. Camuzcuoglu H, Arioz DT, Toy H, et al. Serum paraoxonase and arylesterase activities in patients with epithelial ovarian cancer. Gynecol Oncol. 2009;112(3):481-5.
  36. Faridvand Y, Oskuyi AE, Khadem-Ansari MH. Serum 8-isoprostane levels and paraoxonase 1 activity in patients with stage I multiple myeloma. Redox Rep. 2016;21(5):204-8.
  37. Jin Y, Li Q, Qiu J, et al. Downregulation of paraoxonase 3 contributes to aggressive human hepatocellular carcinoma progression and associates with poor prognosis. Tumour Biol. 2016;37(10):14193-203.
  38. Korkmaz H, Tabur S, Ozkaya M, et al. Paraoxonase and arylesterase activities in patients with papillary thyroid cancer. Scand J Clin Lab Invest. 2015;75(3):259-64.
  39. Malik UU, Siddiqui IA, Hashim Z, et al. Measurement of serum paraoxonase activity and MDA concentrations in patients suffering with oral squamous cell carcinoma. Clin Chim Acta. 2014;430:38-42.
  40. Metin ZB, Aydin S, Unur M, et al. Oral squamous cell carcinoma and serum paraoxonase 1. J Laryngol Otol. 2013;127(12):1208-13.
  41. Sehitogullari A, Aslan M, Sayir F, et al. Serum paraoxonase-1 enzyme activities and oxidative stress levels in patients with esophageal squamous cell carcinoma. Redox Rep. 2014;19(5):199-205.
  42. Malik A, Afaq F, Sarfaraz S, et al. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A. 2005;102(41):14813-8.
  43. Adhami VM, Siddiqui IA, Syed DN, et al. Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model. Carcinogenesis. 2012;33(3):644-51.
  44. Ming DS, Pham S, Deb S, et al. Pomegranate extracts impact the androgen biosynthesis pathways in prostate cancer models in vitro and in vivo. J Steroid Biochem Mol Biol. 2014;143:19-28.
  45. Rettig MB, Heber D, An J, et al. Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer Ther. 2008;7(9):2662-71.
  46. Seeram NP, Aronson WJ, Zhang Y, et al. Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. J Agric Food Chem. 2007;55(19):7732-7.
  47. Pantuck AJ, Leppert JT, Zomorodian N, et al. 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.
  48. Paller CJ, Ye X, Wozniak PJ, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis. 2013;16(1):50-5.
  49. Available at: https://www.cdc.gov/cancer/breast/statistics/index.htm. Accessed 14 March, 2018.
  50. Mandal A, Bishayee A. Mechanism of Breast Cancer Preventive Action of Pomegranate: Disruption of Estrogen Receptor and Wnt/beta-Catenin Signaling Pathways. Molecules. 2015;20(12):22315-28.
  51. Rocha A, Wang L, Penichet M, et al. Pomegranate juice and specific components inhibit cell and molecular processes critical for metastasis of breast cancer. Breast Cancer Res Treat. 2012;136(3):647-58.
  52. Seidi K, Jahanban-Esfahlan R, Abasi M, et al. Anti Tumoral Properties of Punica granatum (Pomegranate) Seed Extract in Different Human Cancer Cells. Asian Pac J Cancer Prev. 2016;17(3):1119-22.
  53. Modaeinama S, Abasi M, Abbasi MM, et al. Anti Tumoral Properties of Punica Granatum (Pomegranate) Peel Extract on Different Human Cancer Cells. Asian Pac J Cancer Prev. 2015;16(14):5697-701.
  54. Sturgeon SR, Ronnenberg AG. Pomegranate and breast cancer: possible mechanisms of prevention. Nutr Rev. 2010;68(2):122-8.
  55. Available at: https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html. Accessed 15 March, 2018.
  56. Nunez-Sanchez MA, Garcia-Villalba R, Monedero-Saiz T, et al. Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol Nutr Food Res. 2014;58(6):1199-211.
  57. Kohno H, Suzuki R, Yasui Y, et al. Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats. Cancer Sci. 2004;95(6):481-6.
  58. Waly MI, Ali A, Guizani N, et al. Pomegranate (Punica granatum) peel extract efficacy as a dietary antioxidant against azoxymethane-induced colon cancer in rat. Asian Pac J Cancer Prev. 2012;13(8):4051-5.
  59. Saruwatari A, Okamura S, Nakajima Y, et al. Pomegranate juice inhibits sulfoconjugation in Caco-2 human colon carcinoma cells. J Med Food. 2008;11(4):623-8.
  60. Nunez-Sanchez MA, Gonzalez-Sarrias A, Garcia-Villalba R, et al. Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial. J Nutr Biochem. 2017;42:126-33.
  61. Nunez-Sanchez MA, Davalos A, Gonzalez-Sarrias A, et al. MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: Critical issues to discern between modulatory effects and potential artefacts. Mol Nutr Food Res. 2015;59(10):1973-86.
;