Cranberry Extract and Cancer

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The anticancer activity of cranberry has not yet been tested in humans, though preclinical data suggest that cranberry extract may help to treat cancer.
The anticancer activity of cranberry has not yet been tested in humans, though preclinical data suggest that cranberry extract may help to treat cancer.

The health benefits of cranberry, an evergreen shrub of the Vaccinium genus, is commonly thought of as preventing or treating urinary tract infections. There are, however, multiple in vitro studies that suggest cranberry may also have anticancer effects. No in-human studies have been conducted to evaluate cranberry for the treatment of cancer.

In Vitro Data

Treatment with a flavanoid-rich fraction of cranberry extract, including proanthocyanidins, resulted in inhibition of growth for multiple different cell lines including in prostate, lung, esophageal, ovarian, and bladder cancer, as well as platinum-resistant ovarian, neuroblastoma, and prostate cancer cell lines.1-7

Treatment with cranberry extract resulted in inhibition of growth for multiple different cell lines including oral, breast, colon, prostate, gastric, and oral cancer.8-12 Cranberry extract also induced apoptosis of cell lines in some studies.12-14

Triterpenoid esters isolated from cranberry inhibited the growth of breast, cervical, and prostate cancer cell lines.15,16

Some studies demonstrated a synergistic effect of treatment with cranberry extract or fractions with chemotherapy in cancer cell lines.6,7

Several studies suggest potential mechanisms for the antitumor properties of cranberry, including cell cycle arrest at the G0/G1 phase, G1 checkpoint, or at G2/M phase; TNF-induced activation of NFκB; inhibition of metalloproteinases; decreased expression of PI3K and AKT; reduced translocation of NFκB to the nucleus; decreased expression of VEGF and EGFR; miRNA modulation; reactive oxygen species generation.8-20

Preclinical Data

Treatment with a flavanoid-rich fraction of cranberry extract resulted in growth inhibition of explant tumors of U87, HT-29, and DU145, as well as regression of some DU145 tumors in mice.21

Intraperitoneal injection of a cranberry extract inhibited growth of lymphoma and increased production of anti-lymphoma antibodies in mice.22

Treatment of mice gastric tumor xenografts with cranberry extract delayed time to tumor growth, and resulted in smaller tumors compared with control.11 Other studies demonstrated inhibition of tumor xenografts in rodent models of colon, esophagus, glioblastoma, lymphoma, prostate, and stomach cancers.23

A prevention study demonstrated that cranberry juice concentrate resulted in dose-dependent prevention of chemically-induced bladder lesions in rats.24

In-human Studies

A double-blind study randomly assigned 64 patients with prostate cancer to receive 1500 mg of dry cranberry fruit powder or placebo daily for at least 21 days prior to undergoing radical prostatectomy.

The cranberry arm experienced a significant 22.5% decrease in prostate-specific antigen compared with 0.9% with placebo (P < .05) immediately prior to surgery. There were no differences, however, in prostate tissue markers.25

Conclusions

A wealth of in vitro and preclinical data suggest that cranberry extracts and isolated fractions may have anticancer activity. Its anticancer activity, however, has not yet been tested in humans. In-human studies are needed to determine cranberry's efficacy as a cancer therapy.

References

  1. Ferguson PJ, Kurowska E, Freeman DJ, Chambers AF, Koropatnick DJ. A flavanoid fraction from cranberry extract inhibits proliferation of human tumor cell lines. J Nutr. 2004;134:1529-35.
  2. Kresty LA, Howell AB, Baird M. Cranberry proanthocyanidins induce apoptosis and inhibit acid-induced proliferation of human esophageal adenocarcinoma cells. J Agric Food Chem. 2008;56:676-80. doi: 10.1021/jf071997t
  3. Kresty LA, Clarke J, Ezell K, Exum A, Howell AB, Guettouche T. MicroRNA alterations in Barrett's esophagus, esophageal adenocarcinoma, and esophageal adenocarcinoma cell lines following cranberry extract treatment: insights for chemoprevention. J Carcinog. 2011;10:34. doi: 10.4103/1477-3163.91110
  4. Kresty LA, Weh KM, Zeyzus-Johns B, Perez LN, Howell AB. Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation. Oncotarget. 2015;6:33438-55.
  5. Prasain JK, Rajbhandari R, Keeton AB, Piazza GA, Barnes S. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells. Food Funct. 2016;7:4012-9. doi: 10.1039/c6fo00499g
  6. Wang Y, Han Z, Chen E, et al. The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells. Intl J Oncol. 2015;46:1924-34. doi: 10.3892/ijo.2015.2931
  7. Singh AP, Singh RK, Kim KK, et al. Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin. Phytother Res. 2009;23:1066-74. doi: 10.1002/ptr.2667
  8. Seeram NP, Adam LS, Zhang Y, Lee R, et al. Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. J Agric Food Chem. 2006;54:9329-39. doi: 10.1021/jf061750g
  9. Sun J, Hai Liu R. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells. Cancer Lett. 2016;241:124-34. doi: 10.1016/j.canlet.2005.10.027
  10. Boivin D, Blanchette M, Barrette S, Moghrabi A, Béliveau R. Inhibition of cancer cell proliferation and suppression of TNF-induced activation of NFκB by edible berry juice. Anticancer Res. 2007;27:937-48.
  11. Liu M, Lin LQ, Song BB, et al. Cranberry phytochemical extract inhibits SGC-7901 cell growth and human tumor xenografts in Balb/c nu/nu mice. J Agric Food Chem. 2009;57:762-8. doi: 10.1021/jf802780k
  12. Chatelain K, Phippen S, McCabe J, Teeters CA, O'Malley S, Kingsley K. Cranberry and grape seed extracts inhibit proliferative phenotype of oral squamous cell carcinomas. Evid Based Complement Alternat Med. 2011;2011:467691. doi: 10.1093/ecam/nen047
  13. MacLean MA, Scott BE, Deziel BA, et al. North American cranberry (Vaccinium macrocarpon) stimulates apoptotic pathways in DU145 human prostate cancer cells in vitro. Nutr Cancer. 2011;63:109-20. doi: 10.1080/01635581.2010.516876
  14. Singh AP, Lange TS, Kim KK, et al. Purified cranberry proanthocyanidins (PAC-1A) cause proapoptotic signaling, ROS generation, cyclophosphamide retention and cytotoxicity in high-risk neuroblastoma cells. Intl J Oncol. 2012;40:99-108. doi: 10.3892/ijo.2011.1225
  15. Murphy BT, MacKinnon SL, Yan X, Hammond GB, Vaisberg AJ, Neto CC. Identification of triterpene hydroxycinnamates with in vitro antitumor activity from whole cranberry fruit (Vaccinium macrocarpon). J Agric Food Chem. 2003;51:3541-5. doi: 10.1021/jf034114g
  16. Kondo M, MacKinnon SL, Craft CC, Matchett MD, Hurta RA, Neto CC. Ursolic acid and its esters: occurnece in cranberries and other Vaccinium fruit and effects on matrix metalloproteinase activity in DU145 prostate tumor cells. J Sci Food Agric. 2011;91:789-96. doi: 10.1002/jsfa.4330
  17. Déziel B, MacPhee J, Patel K, et al. American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators. Food Funct. 2012;3:556-64. doi: 10.1039/c2fo10145a
  18. Kim KK, Singh AP, Singh RK, et al. Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells. Intl J Oncol. 2012;40:227-35. doi: 10.3892/ijo.2011.1198
  19. Déziel BA, Patel K, Neto C, Gottschall-Pass K, Hurta RA. 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. J Cell Biochem. 2010;111:742-54. doi: 10.1002/jcb.22761
  20. Weh KM Aiyer HS, Howell AB, Kresty LA. Cranberry proanthocyanidins modulate reactive oxygen species in Barett's and esophageal adenocarcinoma cell lines. J Berry Res. 2016;6:125-36. doi: 10.3233/JBR-160122
  21. Ferguson PJ, Kurowska EM, Freeman DJ, Chambers AF, Koropatnick J. In vivo inhibition of growth of human tumor lines by flavonoid fractions from cranberry extract. Nutr Cancer. 2006;56:86-94. doi: 10.1207/s15327914nc5601_12
  22. Hochman N, Houri-Haddad Y, Koblinski J, et al. Cranberry juice constituents impair lymphoma growth and augment the generation of antilymphoma antibodies in syngeneic mice. Nutr Cancer. 2008;60:511-7. doi: 10.1080/01635580801956493
  23. Weh KM, Clarke J, Kresty LA. Cranberries and cancer: an update of preclinical studies evaluating the cancer inhibitory potential of cranberry and cranberry derived constituents. Antioxidants. 2016;5:27. doi: 10.3390/antiox5030027
  24. Prasain JK, Jones K, Moore R, et al. Effect of cranberry juice concentrate on chemically-induced urinary bladder cancers. Oncol Rep. 2008;19:1565-70.
  25. Student V, Vidlar A, Bouchal J, et al. Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160:559-565. doi: 10.5507/bp.2016.056

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