Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid

Overview

Journal Nutrients

Date 2018 Nov 17

PMID 30441769

Citations 76

Authors

Claudia Ceci

Pedro M Lacal

Lucio Tentori

Maria Gabriella De Martino

Roberto Miano

Grazia Graziani

Affiliations

Soon will be listed here.

Abstract

Ellagic acid (EA) is a naturally occurring polyphenolic compound endowed with strong antioxidant and anticancer properties that is present in high quantity in a variety of berries, pomegranates, and dried fruits. The antitumor activity of EA has been mostly attributed to direct antiproliferative and apoptotic effects. Moreover, EA can inhibit tumour cell migration, extra-cellular matrix invasion and angiogenesis, all processes that are crucial for tumour infiltrative behaviour and the metastatic process. In addition, EA may increase tumour sensitivity to chemotherapy and radiotherapy. The aim of this review is to summarize the in vitro and in vivo experimental evidence supporting the anticancer activity of pure EA, its metabolites, and EA-containing fruit juice or extracts in a variety of solid tumour models. The EA oral administration as supportive therapy to standard chemotherapy has been recently evaluated in small clinical studies with colorectal or prostate cancer patients. Novel formulations with improved solubility and bioavailability are expected to fully develop the therapeutic potential of EA derivatives in the near future.

Citing Articles

Antiangiogenic Potential of Pomegranate Extracts.

Tornese R, Montefusco A, Placi R, Semeraro T, Durante M, De Caroli M Plants (Basel). 2024; 13(23).

PMID: 39683144 PMC: 11644541. DOI: 10.3390/plants13233350.

A recent update on the connection between dietary phytochemicals and skin cancer: emerging understanding of the molecular mechanism.

Singh H, Mishra A, Mohanto S, Kumar A, Mishra A, Amin R Ann Med Surg (Lond). 2024; 86(10):5877-5913.

PMID: 39359831 PMC: 11444613. DOI: 10.1097/MS9.0000000000002392.

Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions.

Chauhan A, Yadav M, Chauhan R, Basniwal R, Pathak V, Ranjan A Oncol Ther. 2024; 12(4):685-699.

PMID: 39222186 PMC: 11574235. DOI: 10.1007/s40487-024-00296-1.

Metal-Organic Frameworks: Unconventional Nanoweapons against COVID.

Alvarez-Miguel I, Fodor B, Lopez G, Biglione C, Svensson Grape E, Ken Inge A ACS Appl Mater Interfaces. 2024; 16(25):32118-32127.

PMID: 38862123 PMC: 11212624. DOI: 10.1021/acsami.4c06174.

Promising Approaches in Plant-Based Therapies for Thyroid Cancer: An Overview of In Vitro, In Vivo, and Clinical Trial Studies.

Kaczmarzyk I, Nowak-Perlak M, Wozniak M Int J Mol Sci. 2024; 25(8).

PMID: 38674046 PMC: 11050626. DOI: 10.3390/ijms25084463.

References

Crocetti E, Trama A, Stiller C, Caldarella A, Soffietti R, Jaal J . Epidemiology of glial and non-glial brain tumours in Europe. Eur J Cancer. 2012; 48(10):1532-42. DOI: 10.1016/j.ejca.2011.12.013. View

Lipinska L, Klewicka E, Sojka M . The structure, occurrence and biological activity of ellagitannins: a general review. Acta Sci Pol Technol Aliment. 2014; 13(3):289-99. DOI: 10.17306/j.afs.2014.3.7. View

Hussein R, Khalifa F . The protective role of ellagitannins flavonoids pretreatment against N-nitrosodiethylamine induced-hepatocellular carcinoma. Saudi J Biol Sci. 2014; 21(6):589-96. PMC: 4250480. DOI: 10.1016/j.sjbs.2014.03.004. View

Umesalma S, Sudhandiran G . Ellagic acid prevents rat colon carcinogenesis induced by 1, 2 dimethyl hydrazine through inhibition of AKT-phosphoinositide-3 kinase pathway. Eur J Pharmacol. 2011; 660(2-3):249-58. DOI: 10.1016/j.ejphar.2011.03.036. View

Gonzalez-Sarrias A, Tome-Carneiro J, Bellesia A, Tomas-Barberan F, Espin J . The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells. Food Funct. 2015; 6(5):1460-9. DOI: 10.1039/c5fo00120j. View

Liu H, Zeng Z, Wang S, Li T, Mastriani E, Li Q . 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):990-999. PMC: 5718784. DOI: 10.1080/15384047.2017.1394542. View

Xu W, Xu J, Wang T, Liu W, Wei H, Yang X . Ellagic acid and Sennoside B inhibit osteosarcoma cell migration, invasion and growth by repressing the expression of c-Jun. Oncol Lett. 2018; 16(1):898-904. PMC: 6019914. DOI: 10.3892/ol.2018.8712. View

Wang L, Ho J, Glackin C, Martins-Green M . Specific pomegranate juice components as potential inhibitors of prostate cancer metastasis. Transl Oncol. 2012; 5(5):344-55. PMC: 3470115. DOI: 10.1593/tlo.12190. View

Do Carmo Barbosa Mendes De Vasconcelos M, Bennett R, Rosa E, Ferreira Cardoso J . Primary and secondary metabolite composition of kernels from three cultivars of Portuguese chestnut (Castanea sativa Mill.) at different stages of industrial transformation. J Agric Food Chem. 2007; 55(9):3508-16. DOI: 10.1021/jf0629080. View

10.

Larrosa M, Gonzalez-Sarrias A, Garcia-Conesa M, Tomas-Barberan F, Espin J . Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J Agric Food Chem. 2006; 54(5):1611-20. DOI: 10.1021/jf0527403. View

11.

Vanella L, Barbagallo I, Acquaviva R, Di Giacomo C, Cardile V, Abraham N . Ellagic acid: cytodifferentiating and antiproliferative effects in human prostatic cancer cell lines. Curr Pharm Des. 2012; 19(15):2728-36. DOI: 10.2174/1381612811319150008. View

12.

Engelke L, Hamacher A, Proksch P, Kassack M . Ellagic Acid and Resveratrol Prevent the Development of Cisplatin Resistance in the Epithelial Ovarian Cancer Cell Line A2780. J Cancer. 2016; 7(4):353-63. PMC: 4749356. DOI: 10.7150/jca.13754. View

13.

Seeram N, Henning S, Zhang Y, Suchard M, Li Z, Heber D . Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. J Nutr. 2006; 136(10):2481-5. DOI: 10.1093/jn/136.10.2481. View

14.

Falsaperla M, Morgia G, Tartarone A, Ardito R, Romano G . Support ellagic acid therapy in patients with hormone refractory prostate cancer (HRPC) on standard chemotherapy using vinorelbine and estramustine phosphate. Eur Urol. 2005; 47(4):449-54. DOI: 10.1016/j.eururo.2004.12.001. View

15.

Tennant D, Davidson J, Day A . Phytonutrient intakes in relation to European fruit and vegetable consumption patterns observed in different food surveys. Br J Nutr. 2014; 112(7):1214-25. PMC: 4189118. DOI: 10.1017/S0007114514001950. View

16.

Wada L, Ou B . Antioxidant activity and phenolic content of Oregon caneberries. J Agric Food Chem. 2002; 50(12):3495-500. DOI: 10.1021/jf011405l. View

17.

Tentori L, Vergati M, Muzi A, Levati L, Ruffini F, Forini O . Generation of an immortalized human endothelial cell line as a model of neovascular proliferating endothelial cells to assess chemosensitivity to anticancer drugs. Int J Oncol. 2005; 27(2):525-35. View

18.

Chen H, Bai M, Zhang T, Li G, Liu M . Ellagic acid induces cell cycle arrest and apoptosis through TGF-β/Smad3 signaling pathway in human breast cancer MCF-7 cells. Int J Oncol. 2015; 46(4):1730-8. DOI: 10.3892/ijo.2015.2870. View

19.

Vogel A, Cervantes A, Chau I, Daniele B, Llovet J, Meyer T . Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4):iv238-iv255. DOI: 10.1093/annonc/mdy308. View

20.

Anderson M . Update on Survival in Osteosarcoma. Orthop Clin North Am. 2015; 47(1):283-92. DOI: 10.1016/j.ocl.2015.08.022. View