Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs

Jelena Torić 1 , Ana Karković Marković 1 , Cvijeta Jakobušić Brala 1 and Monika Barbarić 1
View More View Less
  • 1 University of Zagreb, 10000, Zagreb, Croatia
Volume/Issue:
Volume 69: Issue 4
Published online:
21 Oct 2019
Pages:
461–482
DOI:
https://doi.org/10.2478/acph-2019-0052
Open access

Abstract

Cancer presents one of the leading causes of death in the world. Current treatment includes the administration of one or more anticancer drugs, commonly known as chemotherapy. The biggest issue concerning the chemotherapeutics is their toxicity on normal cells and persisting side effects. One approach to the issue is chemoprevention and the other one is the discovery of more effective drugs or drug combinations, including combinations with polyphenols. Olive oil polyphenols (OOPs), especially hydroxytyrosol (HTyr), tyrosol (Tyr) and their derivatives oleuropein (Ole), oleacein and oleocanthal (Oc) express anticancer activity on different cancer models. Recent studies report that phenolic extract of virgin olive oil may be more effective than the individual phenolic compounds. Also, there is a growing body of evidence about the combined treatment of OOPs with various anticancer drugs, such as cisplatin, tamoxifen, doxorubicin and others. These novel approaches may present an advanced strategy in the prevention and treatment of cancer.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. WHO Cancer WHO.; Accessed May 21 2019 from http://www.who.int/cancer/en/

  • 2. What Is Cancer? National Cancer Institute; Accessed May 21 2019 from https://www.cancer.gov/about-cancer/understanding/what-is-cancer

  • 3. N. A. Lobo Y. Shimono D. Qian and M. F. Clarke The biology of cancer stem cells Annu. Rev. Cell Dev. Biol. 23 (2007) 675–699; https://doi.org/10.1146/annurev.cellbio.22.010305.104154

  • 4. F. Bray J. Ferlay I. Soerjomataram R. L. Siegel L. A. Torre and A. Jemal Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA-Cancer J. Clin. 68 (2018) 394–424; https://doi.org/10.3322/caac.21492

  • 5. T. Nabekura Overcoming multidrug resistance in human cancer cells by natural compounds Toxins 2 (2010) 1207–1224; https://doi.org/10.3390/toxins2061207

  • 6. M. Fantini M. Benvenuto L. Masuelli G. Frajese I. Tresoldi A. Modesti and R. Bei In vitro and in vivo antitumoral effects of combinations of polyphenols or polyphenols and anticancer drugs: perspectives on cancer treatment Int. J. Mol. Sci. 16 (2015) 9236–9282; https://doi.org/10.3390/ijms16059236

  • 7. The 10 most common chemotherapy side effects Medical News Today.; Accessed May 21 2019 from https://www.medicalnewstoday.com/articles/323485.php

  • 8. U. Lewandowska S. Gorlach K. Owczarek E. Hrabec and K. Szewczyk Synergistic interactions between anticancer chemotherapeutics and phenolic compounds and anticancer synergy between polyphenols Postepy. Hig. Med. Dosw. (Online) 68 (2014) 528–540.

  • 9. C. Manach G. Williamson C. Morand A. Scalbert and C. Rémésy Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies Am. J. Clin. Nutr. 81 (2005) 230S–242S; https://doi.org/10.1093/ajcn/81.1.230S

  • 10. G. Williamson and C. Manach Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies Am. J. Clin. Nutr. 81 (2005) 243S–255S; https://doi.org/10.1093/ajcn/81.1.243S

  • 11. H.-H. S. Chow and I. A. Hakim Pharmacokinetic and chemoprevention studies on tea in humans Pharmacol. Res. (2011) S1043661811001435; https://doi.org/10.1016/j.phrs.2011.05.007

  • 12. A. Rodriguez-Mateos D. Vauzour C. G. Krueger D. Shanmuganayagam J. Reed L. Calani P. Mena D. Del Rio and A. Crozier Bioavailability bioactivity and impact on health of dietary flavonoids and related compounds: an update Arch. Toxicol. 88 (2014) 1803–1853; https://doi.org/10.1007/s00204-014-1330-7

  • 13. T. M. de Kok S. G. van Breda and M. M. Manson Mechanisms of combined action of different chemopreventive dietary compounds: A review Eur. J. Nutr. 47 (2008) 51–59; https://doi.org/10.1007/s00394-008-2006-y

  • 14. H. Wagner Synergy research: Approaching a new generation of phytopharmaceuticals Fitoterapia 82 (2011) 34–37; https://doi.org/10.1016/j.fitote.2010.11.016

  • 15. K. Nurgali R. T. Jagoe and R. Abalo Editorial: Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae? Front. Pharmacol. 9 (2018) 245; https://doi.org/10.3389/fphar.2018.00245

  • 16. D. Shukla R. Rawal and N. Jain A brief review on plant-derived natural compounds as an anti-cancer agents Int. J. Herbal Med. 6 (2018) 28–36.

  • 17. A. K. Garg T. A. Buchholz and B. B. Aggarwal Chemosensitization and radiosensitization of tumors by plant polyphenols Antioxid. Redox Signal. 7 (2005) 1630–1647; https://doi.org/10.1089/ars.2005.7.1630

  • 18. H. Yang K. Landis-Piwowar D. Chen V. Milacic and Q. Dou Natural compounds with proteasome inhibitory activity for cancer prevention and treatment Curr. Protein Pept. Sci. 9 (2008) 227–239; https://doi.org/10.2174/138920308784533998

  • 19. L. G. Korkina C. De Luca V. A. Kostyuk and S. Pastore Plant polyphenols and tumors: from mechanisms to therapies prevention and protection against toxicity of anti-cancer treatments Curr. Med. Chem. 16 (2009) 3943–3965; https://doi.org/10.2174/092986709789352312

  • 20. J. Węsierska-Gądek M. P. Kramer and M. Maurer Resveratrol modulates roscovitine-mediated cell cycle arrest of human MCF-7 breast cancer cells Food Chem. Toxicol. 46 (2008) 1327–1333; https://doi.org/10.1016/j.fct.2007.09.004

  • 21. W. Zhou X. Feng Han Han S. Guo and G. Wang Synergistic effects of combined treatment with histone deacetylase inhibitor suberoylanilide hydroxamic acid and TRAIL on human breast cancer cells Sci. Rep. 6 (2016); https://doi.org/10.1038/srep28004

  • 22. C.-G. Wang W.-N. Yao B. Zhang J. Hua D. Liang and H.-S. Wang Lung cancer and matrix metal-loproteinases inhibitors of polyphenols from Selaginella tamariscina with suppression activity of migration Bioorg. Med. Chem. Lett. 28 (2018) 2413–2417; https://doi.org/10.1016/j.bmcl.2018.06.024

  • 23. R. Fabiani Anti-cancer properties of olive oil secoiridoid phenols: a systematic review of in vivo studies Food Funct. 7 (2016) 4145–4159; https://doi.org/10.1039/C6FO00958A

  • 24. L. Parkinson and S. Cicerale The health benefiting mechanisms of virgin olive oil phenolic compounds Molecules 21 (2016) 1734; https://doi.org/10.3390/molecules21121734

  • 25. M. Gorzynik-Debicka P. Przychodzen F. Cappello A. Kuban-Jankowska A. Marino Gammazza N. Knap M. Wozniak and M. Gorska-Ponikowska Potential health benefits of olive oil and plant polyphenols Int. J. Mol. Sci. 19 (2018) 547; https://doi.org/10.3390/ijms19030686

  • 26. M. Celano V. Maggisano S. M. Lepore D. Russo and S. Bulotta Secoiridoids of olive and derivatives as potential coadjuvant drugs in cancer: A critical analysis of experimental studies Pharmacol. Res. 142 (2019) 77–86; https://doi.org/10.1016/j.phrs.2019.01.045

  • 27. J. Delgado-Lista P. Perez-Martinez J. F. Alcala-Diaz A. I. Perez-Caballero F. Gomez-Delgado F. Fuentes G. Quintana-Navarro F. Lopez-Segura A. M. Ortiz-Morales N. Delgado-Casado E. M. Yubero-Serrano A. Camargo C. Marin F. Rodriguez-Cantalejo P. Gomez-Luna J. M. Ordovas J. Lopez-Miranda and F. Perez-Jimenez CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale methods and baseline characteristics: A clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients Am. Heart J. 177 (2016) 42–50; https://doi.org/10.1016/j.ahj.2016.04.011

  • 28. S. Garcia-Calzon M. A. Martinez-Gonzalez C. Razquin F. Aros J. Lapetra J. Alfredo Martinez G. Zalba and A. Marti Mediterranean diet and telomere length in high cardiovascular risk subjects from the PREDIMED-NAVARRA study Clin. Nutr. 35 (2016) 1399–1405; https://doi.org/10.1016/j.clnu.2016.03.013

  • 29. A. Medina-Remon R. Casas A. Tressserra-Rimbau E. Ros M. A. Martinez-Gonzalez M. Fito D. Corella J. Salas-Salvado R. M. Lamuela-Raventos and R. Estruch Polyphenol intake from a Mediterranean diet decreases inflammatory biomarkers related to atherosclerosis: a substudy of the PREDIMED trial. Br. J. Clin. Pharmacol. 83 (2017) 114–128; https://doi.org/10.1111/bcp.12986

  • 30. Commission Regulation (EU) No 432/2012 of 16 May 2012 establishing a list of permitted health claims made on foods other than those referring to the reduction of disease risk and to children’s development and health Text with EEA relevance (n.d.) 40.

  • 31. J. A. Menendez A. Vazquez-Martin R. Colomer J. Brunet A. Carrasco-Pancorbo R. Garcia-Villalba A. Fernandez-Gutierrez and A. Segura-Carretero Olive oil’s bitter principle reverses acquired autoresistance to trastuzumab (HerceptinTM) in HER2-overexpressing breast cancer cells BMC Cancer 7 (2007); https://doi.org/10.1186/1471-2407-7-80

  • 32. J. Ferlay I. Soerjomataram R. Dikshit S. Eser C. Mathers M. Rebelo D. M. Parkin D. Forman and F. Bray Cancer incidence and mortality worldwide: Sources methods and major patterns in GLOBOCAN 2012: Globocan 2012 Int. J. Cancer 136 (2015) E359–E386; https://doi.org/10.1002/ijc.29210

  • 33. A. Ahmad Farooqi S. Fayyaz A. Silva A. Sureda S. Nabavi A. Mocan S. Nabavi and A. Bishayee Oleuropein and cancer chemoprevention: The link is hot Molecules 22 (2017) 705; https://doi.org/10.3390/molecules22050705

  • 34. M. A. Khanfar S. K. Bardaweel M. R. Akl and K. A. El Sayed Olive oil-derived oleocanthal as potent inhibitor of mammalian target of rapamycin: Biological evaluation and molecular modeling studies: oleocanthal is a potent mTOR inhibitor Phytother. Res. 29 (2015) 1776–1782; https://doi.org/10.1002/ptr.5434

  • 35. J. Calahorra E. Martínez-Lara C. De Dios and E. Siles Hypoxia modulates the antioxidant effect of hydroxytyrosol in MCF-7 breast cancer cells PLOS ONE 13 (2018) e0203892; https://doi.org/10.1371/journal.pone.0203892

  • 36. Y. Z. H.-Y. Hashim J. Worthington P. Allsopp N. G. Ternan E. M. Brown M. J. McCann I. R. Rowland S. Esposto M. Servili and C. I. R. Gill Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo Food Funct. 5 (2014) 1513–1519; https://doi.org/10.1039/c4fo00090k

  • 37. H. Zubair A. Bhardwaj A. Ahmad S. K. Srivastava M. A. Khan G. K. Patel S. Singh and A. P. Singh Hydroxytyrosol induces apoptosis and cell cycle arrest and suppresses multiple oncogenic signaling pathways in prostate cancer cells Nutrit. Cancer 69 (2017) 932–942; https://doi.org/10.1080/01635581.2017.1339818

  • 38. H. Song D. Y. Lim J. I. Jung H. J. Cho S. Y. Park G. T. Kwon Y.-H. Kang K. W. Lee M.-S. Choi and J. H. Y. Park Dietary oleuropein inhibits tumor angiogenesis and lymphangiogenesis in the B16F10 melanoma allograft model: a mechanism for the suppression of high-fat diet-induced solid tumor growth and lymph node metastasis Oncotarget 8 (2017) 32027–32042; https://doi.org/10.18632/oncotarget.16757

  • 39. R. Fabiani P. Rosignoli A. D. Bartolomeo R. Fuccelli M. Servili G. F. Montedoro and G. Morozzi Oxidative DNA damage is prevented by extracts of olive oil hydroxytyrosol and other olive phenolic compounds in human blood mononuclear cells and HL60 cells J. Nutr. 138 (2008) 1411–1416. https://doi.org/10.1093/jn/138.8.1411

  • 40. I. Potočnjak M. Škoda E. Pernjak-Pugel M. P. Peršić and R. Domitrović Oral administration of oleuropein attenuates cisplatin-induced acute renal injury in mice through inhibition of ERK signaling Mol. Nutr. Food Res. 60 (2016) 530–541; https://doi.org/10.1002/mnfr.201500409

  • 41. I. O. Sherif and M. M. H. Al-Gayyar Oleuropein potentiates anti-tumor activity of cisplatin against HepG2 through affecting proNGF/NGF balance Life Sci. 198 (2018) 87–93; https://doi.org/10.1016/j.lfs.2018.02.027

  • 42. I. O. Sherif The effect of natural antioxidants in cyclophosphamide-induced hepatotoxicity: Role of Nrf2/HO-1 pathway Int. Immunopharmacol. 61 (2018) 29–36; https://doi.org/10.1016/j.intimp.2018.05.007

  • 43. J. Ruzzolini S. Peppicelli E. Andreucci F. Bianchini A. Scardigli A. Romani G. la Marca C. Nediani and L. Calorini Oleuropein the main polyphenol of Olea europaea leaf extract has an anti-cancer effect on human BRAF melanoma cells and potentiates the cytotoxicity of current chemotherapies Nutrients 10 (2018) 1950; https://doi.org/10.3390/nu10121950

  • 44. N. El-azem M. Pulido-Moran C. L. Ramirez-Tortosa J. L. Quiles F. E. Cara P. Sanchez-Rovira S. Granados-Principal and Mc. Ramirez-Tortosa Modulation by hydroxytyrosol of oxidative stress and antitumor activities of paclitaxel in breast cancer Eur. J. Nutr. 58 (2019) 1203–1211; https://doi.org/10.1007/s00394-018-1638-9

  • 45. A. Coccia L. Mosca R. Puca G. Mangino A. Rossi and E. Lendaro Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells Oncol. Rep. 36 (2016) 3095–3104; https://doi.org/10.3892/or.2016.5150

  • 46. M. H. Elamin A. B. Elmahi M. H. Daghestani E. M. Al-Olayan R. A. Al-Ajmi A. F. Alkhuriji S. S. Hamed and M. F. Elkhadragy Synergistic anti-breast-cancer effects of combined treatment with oleuropein and doxorubicin in vivoAltern. Ther. Health Med. 25 (2019) 17–24.

  • 47. E. Terzuoli G. Nannelli M. Frosini A. Giachetti M. Ziche and S. Donnini Inhibition of cell cycle progression by the hydroxytyrosol–cetuximab combination yields enhanced chemotherapeutic efficacy in colon cancer cells Oncotarget 8 (2017) 83207–83224; https://doi.org/10.18632/oncotarget.20544

  • 48. N. M. Ayoub A. B. Siddique H. Y. Ebrahim M. M. Mohyeldin and K. A. El Sayed The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment Europ. J. Pharmacol. 810 (2017) 100–111; https://doi.org/10.1016/j.ejphar.2017.06.019

  • 49. A. B. Siddique H. Y. Ebrahim M. R. Akl N. M. Ayoub A. A. Goda M. M. Mohyeldin S. K. Nagumalli W. M. Hananeh Y.-Y. Liu S. A. Meyer and K. A. El Sayed (-)-Oleocanthal combined with lapatinib treatment synergized against HER-2 positive breast cancer in vitro and in vivoNutrients 11 (2019) 412; https://doi.org/10.3390/nu11020412

  • 50. R. Ghanbari F. Anwar K. M. Alkharfy A.-H. Gilani and N. Saari Valuable nutrients and functional bioactives in different parts of olive (Olea europaea L.) – A review Int. J. Mol. Sci. 13 (2012) 3291–3340; https://doi.org/10.3390/ijms13033291

  • 51. D. Boskou Olive Oil: Chemistry and Technology 2nd ed. AOCS Publishing. Champaign 2006; https://doi.org/10.1201/9781439832028

  • 52. S. Cicerale X. A. Conlan A. J. Sinclair and R. S. J. Keast Chemistry and health of olive oil phenolics Crit. Rev. Food Sci. Nutr. 49 (2008) 218–236; https://doi.org/10.1080/10408390701856223

  • 53. A. Bendini L. Cerretani A. Carrasco-Pancorbo A. M. Gómez-Caravaca A. Segura-Carretero A. Fernández-Gutiérrez and G. Lercker Phenolic molecules in virgin olive oils: A survey of their sensory properties health effects antioxidant activity and analytical methods. An overview of the last decade Molecules 12 (2007) 1679-1719.

  • 54. C. Jakobušić Brala M. Barbarić A. Karković Marković S. Uršić Biomedicinal Aspects and Activities of Olive Oil Phenolic Compounds in Handbook of Olive Oil: Phenolic Compounds Production and Health Benefits (Ed. J. Miloš) Nova Science Publishers Inc. New York 2017 pp. 47–85. ISBN: 978-1-53612-357-9.

  • 55. S. Rigacci and M. Stefani Nutraceutical properties of olive oil polyphenols. An itinerary from cultured cells through animal models to humans Int. J. Mol. Sci. 17 (2016) 843; https://doi.org/10.3390/ijms17060843

  • 56. H. Shamshoum F. Vlavcheski and E. Tsiani Anticancer effects of oleuropein BioFactors 43 (2017) 517–528; https://doi.org/10.1002/biof.1366

  • 57. M. Imran M. Nadeem S. A. Gilani S. Khan M. W. Sajid and R. M. Amir Antitumor perspectives of oleuropein and its metabolite hydroxytyrosol: Recent updates J. Food Sci. 83 (2018) 1781–1791; https://doi.org/10.1111/1750-3841.14198

  • 58. A. M. Borzì A. Biondi F. Basile S. Luca E. S. D. Vicari and M. Vacante Olive oil effects on colorectal cancer Nutrients 11 (2019) 32; https://doi.org/10.3390/nu11010032

  • 59. A. Di Francesco A. Falconi C. Di Germanio M. V. Micioni Di Bonaventura A. Costa S. Caramuta M. Del Carlo D. Compagnone E. Dainese C. Cifani M. Maccarrone and C. D’Addario Extravirgin olive oil up-regulates CB1 tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms J. Nutr. Biochem. 26 (2015) 250–258; https://doi.org/10.1016/j.jnutbio.2014.10.013

  • 60. Z. K. Hassan M. H. Elamin M. H. Daghestani S. A. Omer E. M. Al-Olayan M. A. Elobeid P. Virk and O. B. Mohammed Oleuropein induces anti-metastatic effects in breast cancer Asian Pac. J. Cancer Prev. 13 (2012) 4555–4559; https://doi.org/10.7314/APJCP.2012.13.9.4555

  • 61. C. I. R. Gill A. Boyd E. McDermott M. McCann M. Servili R. Selvaggini A. Taticchi S. Esposto G. Montedoro H. McGlynn and I. Rowland Potential anti-cancer effects of virgin olive oil phenolson colorectal carcinogenesis models in vitro Int. J. Cancer 117 (2005) 1–7; https://doi.org/10.1002/ijc.21083

  • 62. S. Sánchez-Fidalgo I. Villegas A. Cárdeno E. Talero M. Sánchez-Hidalgo V. Motilva and C. Alarcón de la Lastra Extra-virgin olive oil-enriched diet modulates DSS-colitis-associated colon carcinogenesis in mice Clin. Nutr. 29 (2010) 663–673; https://doi.org/10.1016/j.clnu.2010.03.003

  • 63. A. P. Femia P. Dolara M. Servili S. Esposto A. Taticchi S. Urbani A. Giannini M. Salvadori and G. Caderni No effects of olive oils with different phenolic content compared to corn oil on 12-dimethylhydrazine-induced colon carcinogenesis in rats Eur. J. Nutr. 47 (2008) 329–334; https://doi.org/10.1007/s00394-008-0731-x

  • 64. B. Pampaloni C. Mavilia S. Fabbri A. Romani F. Ieri A. Tanini F. Tonelli and M. L. Brandi In vitro effects of extracts of extra virgin olive oil on human colon cancer cells Nutr. Cancer 66 (2014) 1228–1236; https://doi.org/10.1080/01635581.2014.951727

  • 65. A. Coccia D. Bastianelli L. Mosca R. Monticolo I. Panuccio A. Carbone A. Calogero and E. Lendaro Extra virgin olive oil phenols suppress migration and invasion of T24 human bladder cancer cells through modulation of matrix metalloproteinase-2 Nutr. Cancer 66 (2014) 946–954; https://doi.org/10.1080/01635581.2014.922204

  • 66. B. Polini M. Digiacomo S. Carpi S. Bertini F. Gado G. Saccomanni M. Macchia P. Nieri C. Manera and S. Fogli Oleocanthal and oleacein contribute to the in vitro therapeutic potential of extra virgin oil-derived extracts in non-melanoma skin cancer Toxicol. In Vitro 52 (2018) 243–250; https://doi.org/10.1016/j.tiv.2018.06.021

  • 67. M.-C. López de las Hazas C. Piñol A. Macià and M.-J. Motilva Hydroxytyrosol and the colonic metabolites derived from virgin olive oil intake induce cell cycle arrest and apoptosis in colon cancer cells J. Agric. Food Chem. 65 (2017) 6467–6476; https://doi.org/10.1021/acs.jafc.6b04933

  • 68. R. Fabiani M. V. Sepporta P. Rosignoli A. De Bartolomeo M. Crescimanno and G. Morozzi Anti-proliferative and pro-apoptotic activities of hydroxytyrosol on different tumour cells: the role of extracellular production of hydrogen peroxide Eur. J. Nutr. 51 (2012) 455–464; https://doi.org/10.1007/s00394-011-0230-3

  • 69. L. Sun C. Luo and J. Liu Hydroxytyrosol induces apoptosis in human colon cancer cells through ROS generation Food Funct. 5 (2014) 1909–1914; https://doi.org/10.1039/C4FO00187G

  • 70. P. Rosignoli R. Fuccelli M. V. Sepporta and R. Fabiani In vitro chemo-preventive activities of hydroxytyrosol: The main phenolic compound present in extra-virgin olive oil Food Funct. 7 (2016) 301–307; https://doi.org/10.1039/C5FO00932D

  • 71. E. Terzuoli A. Giachetti M. Ziche and S. Donnini Hydroxytyrosol a product from olive oil reduces colon cancer growth by enhancing epidermal growth factor receptor degradation Mol. Nutr. Food Res. 60 (2016) 519–529; https://doi.org/10.1002/mnfr.201500498

  • 72. B. Zhao Y. Ma Z. Xu J. Wang F. Wang D. Wang S. Pan Y. Wu H. Pan D. Xu L. Liu and H. Jiang Hydroxytyrosol a natural molecule from olive oil suppresses the growth of human hepatocellular carcinoma cells via inactivating AKT and nuclear factor-kappa B pathways Cancer Lett. 347 (2014) 79–87; https://doi.org/10.1016/j.canlet.2014.01.028

  • 73. S. Li Z. Han Y. Ma R. Song T. Pei T. Zheng J. Wang D. Xu X. Fang H. Jiang and L. Liu Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: An in vivo and in vitro study Oncol. Rep. 31 (2014) 145–152; https://doi.org/10.3892/or.2013.2853

  • 74. R. Sirianni A. Chimento A. De Luca I. Casaburi P. Rizza A. Onofrio D. Iacopetta F. Puoci S. Andò M. Maggiolini and V. Pezzi Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation Mol. Nutr. Food Res. 54 (2009) 833–840; https://doi.org/10.1002/mnfr.200900111

  • 75. A. Chimento I. Casaburi C. Rosano P. Avena A. De Luca C. Campana E. Martire M. F. Santolla M. Maggiolini V. Pezzi and R. Sirianni Oleuropein and hydroxytyrosol activate GPER/GPR30-dependent pathways leading to apoptosis of ER-negative SKBR3 breast cancer cells Mol. Nutr. Food Res. 58 (2014) 478–489; https://doi.org/10.1002/mnfr.201300323

  • 76. C. Goldsmith D. Bond H. Jankowski J. Weidenhofer C. Stathopoulos P. Roach and C. Scarlett The olive biophenols oleuropein and hydroxytyrosol selectively reduce proliferation influence the cell cycle and induce apoptosis in pancreatic cancer cells Int. J. Mol. Sci. 19 (2018) 1937; https://doi.org/10.3390/ijms19071937

  • 77. G. Toteda S. Lupinacci D. Vizza R. Bonofiglio E. Perri M. Bonofiglio D. Lofaro A. La Russa F. Leone P. Gigliotti R. A. Cifarelli and A. Perri High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells J. Endocrinol. Invest. 40 (2017) 153–162; https://doi.org/10.1007/s40618-016-0537-2

  • 78. M. Ramírez-Expósito and J. Martínez-Martos Anti-inflammatory and antitumor effects of hydroxytyrosol but not oleuropein on experimental glioma in vivo. A putative role for the reninangiotensin system Biomedicines 6 (2018) 11; https://doi.org/10.3390/biomedicines6010011

  • 79. M. H. Elamin M. H. Daghestani S. A. Omer M. A. Elobeid P. Virk E. M. Al-Olayan Z. K. Hassan O. B. Mohammed and A. Aboussekhra Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells Food Chem. Toxicol. 53 (2013) 310–316; https://doi.org/10.1016/j.fct.2012.12.009

  • 80. L. Liu K. S. Ahn M. K. Shanmugam H. Wang H. Shen F. Arfuso A. Chinnathambi S. A. Alharbi Y. Chang G. Sethi and F. R. Tang Oleuropein induces apoptosis via abrogating NF-κB activation cascade in estrogen receptor-negative breast cancer cells J. Cell. Biochem. 120 (2019) 4504–4513; https://doi.org/10.1002/jcb.27738

  • 81. M. V. Sepporta R. Fuccelli P. Rosignoli G. Ricci M. Servili G. Morozzi and R. Fabiani Oleuropein inhibits tumour growth and metastases dissemination in ovariectomised nude mice with MCF-7 human breast tumour xenografts J. Funct. Foods 8 (2014) 269–273; https://doi.org/10.1016/j.jff.2014.03.027

  • 82. A. Cárdeno M. Sánchez-Hidalgo M. A. Rosillo and C. A. de la Lastra Oleuropein a Secoiridoid Derived from Olive Tree Inhibits the proliferation of human colorectal cancer cell through down-regulation of HIF-1α Nutr. Cancer 65 (2013) 147–156; https://doi.org/10.1080/01635581.2013.741758

  • 83. C.-M. Yan E.-Q. Chai H.-Y. Cai G.-Y. Miao and W. Ma Oleuropein induces apoptosis via activation of caspases and suppression of phosphatidylinositol 3-kinase/protein kinase B pathway in HepG2 human hepatoma cell line Mol. Med. Rep. 11 (2015) 4617–4624; https://doi.org/10.3892/mmr.2015.3266

  • 84. J. Yao J. Wu X. Yang J. Yang Y. Zhang and L. Du Oleuropein induced apoptosis in HeLa cells via a mitochondrial apoptotic cascade associated with activation of the c-Jun NH2-terminal kinase J. Pharmacol. Sci. 125 (2014) 300–311; https://doi.org/10.1254/jphs.14012FP

  • 85. R. Acquaviva C. Di Giacomo V. Sorrenti F. Galvano R. Santangelo V. Cardile S. Gangia N. D’orazio N. G. Abraham and L. Vanella Antiproliferative effect of oleuropein in prostate cell lines Int. J. Oncol. 41 (2012) 31-38; https://doi.org/10.3892/ijo.2012.1428

  • 86. M. Seçme C. Eroğlu Y. Dodurga and G. Bağcı Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells Gene 585 (2016) 93–99; https://doi.org/10.1016/j.gene.2016.03.038

  • 87. C. R. Capo J. Z. Pedersen M. Falconi and L. Rossi Oleuropein shows copper complexing properties and noxious effect on cultured SH-SY5Y neuroblastoma cells depending on cell copper content J. Trace Elem. Med. Biol. 44 (2017) 225–232; https://doi.org/10.1016/j.jtemb.2017.08.002

  • 88. Y. Kimura and M. Sumiyoshi Olive leaf extract and its main component oleuropein prevent chronic ultraviolet B radiation-induced skin damage and carcinogenesis in hairless mice J. Nutr. 139 (2009) 2079–2086; https://doi.org/10.3945/jn.109.104992

  • 89. S. Cao X. Zhu and L. Du P38 MAP kinase is involved in oleuropein-induced apoptosis in A549 cells by a mitochondrial apoptotic cascade Biomed. Pharmacother. 95 (2017) 1425–1435; https://doi.org/10.1016/j.biopha.2017.09.072

  • 90. W. Wang J. Wu Q. Zhang X. Li X. Zhu Q. Wang S. Cao and L. Du Mitochondria-mediated apoptosis was induced by oleuropein in H1299 cells involving activation of p38 MAP kinase J. Cell. Biochem. 120 (2019) 5480–5494; https://doi.org/10.1002/jcb.27827

  • 91. L. Parkinson and R. Keast Oleocanthal a phenolic derived from virgin olive oil: A review of the beneficial effects on inflammatory disease Int. J. Mol. Sci. 15 (2014) 12323–12334; https://doi.org/10.3390/ijms150712323

  • 92. P. Khanal W.-K. Oh H. J. Yun G. M. Namgoong S.-G. Ahn S.-M. Kwon H.-K. Choi and H. S. Choi p-HPEA-EDA a phenolic compound of virgin olive oil activates AMP-activated protein kinase to inhibit carcinogenesis Carcinogenesis 32 (2011) 545–553; https://doi.org/10.1093/carcin/bgr001

  • 93. M. R. Akl N. M. Ayoub M. M. Mohyeldin B. A. Busnena A. I. Foudah Y.-Y. Liu and K. A. E. Sayed Olive phenolics as c-Met inhibitors: (-)-Oleocanthal attenuates cell proliferation invasiveness and tumor growth in breast cancer models PLoS ONE 9 (2014) e97622; https://doi.org/10.1371/journal.pone.0097622

  • 94. A. Elnagar P. Sylvester and K. El Sayed (−)-Oleocanthal as a c-Met inhibitor for the control of metastatic breast and prostate cancers Planta Med. 77 (2011) 1013–1019; https://doi.org/10.1055/s-0030-1270724

  • 95. R. Diez-Bello I. Jardin J. J. Lopez M. El Haouari J. Ortega-Vidal J. Altarejos G. M. Salido S. Salido and J. A. Rosado (−)-Oleocanthal inhibits proliferation and migration by modulating Ca2+ entry through TRPC6 in breast cancer cells Biochim. Biophys. Acta BBA - Mol. Cell Res. 1866 (2019) 474–485; https://doi.org/10.1016/j.bbamcr.2018.10.010

  • 96. S. Fogli C. Arena S. Carpi B. Polini S. Bertini M. Digiacomo F. Gado A. Saba G. Saccomanni M. C. Breschi P. Nieri C. Manera and M. Macchia Cytotoxic activity of oleocanthal isolated from virgin olive oil on human melanoma cells Nutr. Cancer 68 (2016) 873–877; https://doi.org/10.1080/01635581.2016.1180407

  • 97. Y. Gu J. Wang and L. Peng (−)-Oleocanthal exerts anti-melanoma activities and inhibits STAT3 signaling pathway Oncol. Rep. 37 (2017) 483–491; https://doi.org/10.3892/or.2016.5270

  • 98. T. Pei Q. Meng J. Han H. Sun L. Li R. Song B. Sun S. Pan D. Liang and L. Liu (-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma Oncotarget 7 (2016) 43475–43491; https://doi.org/10.18632/oncotarget.9782

  • 99. A. Cusimano D. Balasus A. Azzolina G. Augello M. R. Emma C. Di Sano R. Gramignoli S. C. Strom J. A. Mccubrey G. Montalto and M. Cervello Oleocanthal exerts antitumor effects on human liver and colon cancer cells through ROS generation Int. J. Oncol. 51 (2017) 533–544; https://doi.org/10.3892/ijo.2017.4049

  • 100. M. Scotece R. Gómez J. Conde V. Lopez J. J. Gómez-Reino F. Lago A. B. Smith III and O. Gualillo Oleocanthal inhibits proliferation and MIP-1 expression in human multiple myeloma cells Curr. Med. Chem. 20 (2013) 2467–2475; https://doi.org/10.2174/0929867311320190006

  • 101. J. M. Calderón-Montaño A. Madrona E. Burgos-Morón M. L. Orta S. Mateos J. L. Espartero and M. López-Lázaro Selective cytotoxic activity of new lipophilic hydroxytyrosol alkyl ether derivatives J. Agric. Food Chem. 61 (2013) 5046–5053; https://doi.org/10.1021/jf400796p

  • 102. R. Bernini M. S. Gilardini Montani N. Merendino A. Romani and F. Velotti Hydroxytyrosol-derived compounds: A basis for the creation of new pharmacological agents for cancer prevention and therapy J. Med. Chem. 58 (2015) 9089-9107; https://doi.org/10.1021/acs.jmedchem.5b00669

  • 103. R. Bernini I. Carastro G. Palmini A. Tanini R. Zonefrati P. Pinelli M. L. Brandi and A. Romani Lipophilization of hydroxytyrosol-enriched fractions from Olea europaea L. byproducts and evaluation of the in vitro effects on a model of colorectal cancer cells J. Agric. Food Chem. 65 (2017) 6506–6512; https://doi.org/10.1021/acs.jafc.6b05457

  • 104. S. Bulotta R. Corradino M. Celano J. Maiuolo M. D’Agostino M. Oliverio A. Procopio S. Filetti and D. Russo Antioxidant and antigrowth action of peracetylated oleuropein in thyroid cancer cells J. Mol. Endocrinol. 51 (2013) 181–189; https://doi.org/10.1530/JME-12-0241

  • 105. S. Bulotta R. Corradino M. Celano M. D’Agostino J. Maiuolo M. Oliverio A. Procopio M. Iannone D. Rotiroti and D. Russo Antiproliferative and antioxidant effects on breast cancer cells of oleuropein and its semisynthetic peracetylated derivatives Food Chem. 127 (2011) 1609–1614; https://doi.org/10.1016/j.foodchem.2011.02.025

  • 106. B. A. Busnena A. I. Foudah T. Melancon and K. A. El Sayed Olive secoiridoids and semisynthetic bioisostere analogues for the control of metastatic breast cancer Bioorg. Med. Chem. 21 (2013) 2117–2127; https://doi.org/10.1016/j.bmc.2012.12.050

  • 107. M. M. Mohyeldin M. R. Akl H. Y. Ebrahim A. M. Dragoi S. Dykes J. A. Cardelli and K. A. E. Sayed The oleocanthal-based homovanillyl sinapate as a novel c-Met inhibitor Oncotarget 7 (2016) 32247–32273; https://doi.org/10.18632/oncotarget.8681

  • 108. B. Salehi P. Zucca M. Sharifi-Rad R. Pezzani S. Rajabi W. N. Setzer E. M. Varoni M. Iriti F. Kobarfard and J. Sharifi-Rad Phytotherapeutics in cancer invasion and metastasis Phytother. Res. 32 (2018) 1425–1449; https://doi.org/10.1002/ptr.6087

  • 109. R. Fabiani M. V. Sepporta T. Mazza P. Rosignoli R. Fuccelli A. De Bartolomeo M. Crescimanno A. Taticchi S. Esposto M. Servili and G. Morozzi Influence of cultivar and concentration of selected phenolic constituents on the in vitro chemiopreventive potential of olive oil extracts J. Agric. Food Chem. 59 (2011) 8167–8174; https://doi.org/10.1021/jf201459u

  • 110. T. Kubota S. W. Matsuzaki Y. Hoshiya M. Watanabe M. Kitajima F. Asanuma Y. Yamada J. Koh Antitumor activity of paclitaxel against human breast carcinoma xenografts serially transplanted into nude mice J. Surg. Oncol. 64 (1997) 115-121.

  • 111. S. V. Singh D. Scalamogna H. Xia S. O’Toole D. Roy E. O. Emerson V. Gupta and H. A. Zaren Biochemical characterization of a mitomycin C-resistant human bladder cancer cell line Int. J. Cancer. 65 (1996) 852-857; https://doi.org/10.1002/(SICI)1097-0215(19960315)65:6<852::AID-IJC24>3.0.CO;2-4

  • 112. L. Kelland The resurgence of platinum-based cancer chemotherapy Nat. Rev. Cancer 7 (2007) 573–584; https://doi.org/10.1038/nrc2167

  • 113. S. Cerig F. Geyikoglu M. Bakir S. Colak M. Sonmez K. Koc Hepatoprotective effect of oleuropein against cisplatin-induced liver damage in rat Int. J. Med. Health Sci. 10 (2016) 264–271.

  • 114. F. Geyikoglu H. Isikgoz H. Onalan S. Colak S. Cerig M. Bakir M. Hosseinigouzdagani K. Koc H. S. Erol Y. S. Saglam and S. Yildirim Impact of high-dose oleuropein on cisplatin-induced oxidative stress genotoxicity and pathological changes in rat stomach and lung J. Asian Nat. Prod. Res. 19 (2017) 1214–1231; https://doi.org/10.1080/10286020.2017.1317751

  • 115. M. Bakir F. Geyikoglu K. Koc and S. Cerig Therapeutic effects of oleuropein on cisplatin-induced pancreas injury in rats J. Can. Res. Ther. 14 (2018) 671; https://doi.org/10.4103/jcrt.JCRT_1040_16

  • 116. G. Ventura R. Abbattista C. D. Calvano C. De Ceglie I. Losito F. Palmisano and T. R. Cataldi Tandem mass spectrometry characterization of a conjugate between oleuropein and hydrated cisdiammineplatinum(II) Rapid Commun. Mass Spectrom. 33 (2019) 657–666; https://doi.org/10.1002/rcm.8394

  • 117. P. Przychodzen R. Wyszkowska M. Gorzynik-Debicka T. Kostrzewa A. Kuban-Jankowska and M. Gorska-Ponikowska Anticancer potential of oleuropein the polyphenol of olive oil with 2-methoxyestradiol separately or in combination in human osteosarcoma cells Anticancer Res. 39 (2019) 1243–1251; https://doi.org/10.21873/anticanres.13234

  • 118. U. Ernest H.-Y. Chen M.-J. Xu Y. D. Taghipour M. H. H. Bin Asad R. Rahimi and G. Murtaza Anti-cancerous potential of polyphenol-loaded polymeric nanotherapeutics Molecules 23 (2018) 2787; https://doi.org/10.3390/molecules23112787

  • 119. A. K. Jain K. Thanki and S. Jain Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles: Implications on oral bioavailability antitumor efficacy and drug-induced toxicity Mol. Pharmaceutics 10 (2013) 3459–3474; https://doi.org/10.1021/mp400311j
Cover Image of: Acta Pharmaceutica
Search
Journal information
ISSN:
1846-9558
First Published:
28 Feb 2007
Language:
English
Impact Factor

IMPACT FACTOR 2018: 1.405
5-year IMPACT FACTOR: 1.701

CiteScore 2018: 1.47

SCImago Journal Rank (SJR) 2018: 0.314
Source Normalized Impact per Paper (SNIP) 2018: 0.637

Metrics
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 389 389 160
PDF Downloads 328 328 168