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

1. WHO Cancer, WHO.; Accessed May 21, 2019, from http://www.who.int/cancer/en/Search in Google Scholar

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

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.22.010305.10415410.1146/annurev.cellbio.22.010305.10415417645413Search in Google Scholar

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.2149210.3322/caac.2149230207593Search in Google Scholar

5. T. Nabekura, Overcoming multidrug resistance in human cancer cells by natural compounds, Toxins2 (2010) 1207–1224; https://doi.org/10.3390/toxins206120710.3390/toxins2061207315324122069634Search in Google Scholar

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/ijms1605923610.3390/ijms16059236446358725918934Search in Google Scholar

7. The 10 most common chemotherapy side effects, Medical News Today.; Accessed May 21, 2019, from https://www.medicalnewstoday.com/articles/323485.phpSearch in Google Scholar

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) 528–540.10.5604/17322693.110227824864104Search in Google Scholar

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/81.1.230S10.1093/ajcn/81.1.230S15640486Search in Google Scholar

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/81.1.243S10.1093/ajcn/81.1.243S15640487Search in Google Scholar

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.2011.05.00710.1016/j.phrs.2011.05.007315230621624470Search in Google Scholar

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/s00204-014-1330-710.1007/s00204-014-1330-725182418Search in Google Scholar

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-y10.1007/s00394-008-2006-y18458834Search in Google Scholar

14. H. Wagner, Synergy research: Approaching a new generation of phytopharmaceuticals, Fitoterapia82 (2011) 34–37; https://doi.org/10.1016/j.fitote.2010.11.01610.1016/j.fitote.2010.11.01621075177Search in Google Scholar

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.2018.0024510.3389/fphar.2018.00245587432129623040Search in Google Scholar

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.Search in Google Scholar

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.2005.7.163010.1089/ars.2005.7.163016356126Search in Google Scholar

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/10.2174/13892030878453399810.2174/138920308784533998330315218537678Search in Google Scholar

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/10.2174/09298670978935231210.2174/09298670978935231219747130Search in Google Scholar

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.2007.09.00410.1016/j.fct.2007.09.00417933449Search in Google Scholar

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/srep2800410.1038/srep28004490427727292433Search in Google Scholar

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.2018.06.02410.1016/j.bmcl.2018.06.02429921475Search in Google Scholar

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/C6FO00958A10.1039/C6FO00958ASearch in Google Scholar

24. L. Parkinson and S. Cicerale, The health benefiting mechanisms of virgin olive oil phenolic compounds, Molecules21 (2016) 1734; https://doi.org/10.3390/molecules2112173410.3390/molecules21121734627350027999296Search in Google Scholar

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/ijms1903068610.3390/ijms19030686587754729495598Search in Google Scholar

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.2019.01.04510.1016/j.phrs.2019.01.04530772463Search in Google Scholar

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.2016.04.01110.1016/j.ahj.2016.04.011491062227297848Search in Google Scholar

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.2016.03.01310.1016/j.clnu.2016.03.01327083496Search in Google Scholar

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.1298610.1111/bcp.12986533814727100393Search in Google Scholar

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.Search in Google Scholar

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 (Herceptin^TM) in HER2-overexpressing breast cancer cells, BMC Cancer7 (2007); https://doi.org/10.1186/1471-2407-7-8010.1186/1471-2407-7-80187849317490486Search in Google Scholar

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. Cancer136 (2015) E359–E386; https://doi.org/10.1002/ijc.2921010.1002/ijc.2921025220842Search in Google Scholar

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, Molecules22 (2017) 705; https://doi.org/10.3390/molecules2205070510.3390/molecules22050705615454328468276Search in Google Scholar

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.543410.1002/ptr.5434505127326248874Search in Google Scholar

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 ONE13 (2018) e0203892; https://doi.org/10.1371/journal.pone.020389210.1371/journal.pone.0203892614745930235254Search in Google Scholar

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/c4fo00090k10.1039/c4fo00090k24836598Search in Google Scholar

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. Cancer69 (2017) 932–942; https://doi.org/10.1080/01635581.2017.133981810.1080/01635581.2017.1339818612578128718667Search in Google Scholar

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, Oncotarget8 (2017) 32027–32042; https://doi.org/10.18632/oncotarget.1675710.18632/oncotarget.16757545826628410190Search in Google Scholar

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/138.8.141110.1093/jn/138.8.141118641183Search in Google Scholar

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.20150040910.1002/mnfr.20150040926603374Search in Google Scholar

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.2018.02.02710.1016/j.lfs.2018.02.02729476769Search in Google Scholar

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.2018.05.00710.1016/j.intimp.2018.05.00729800788Search in Google Scholar

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, Nutrients10 (2018) 1950; https://doi.org/10.3390/nu1012195010.3390/nu10121950631680130544808Search in Google Scholar

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/s00394-018-1638-910.1007/s00394-018-1638-929468462Search in Google Scholar

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.2016.515010.3892/or.2016.5150511260827748855Search in Google Scholar

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 vivo, Altern. Ther. Health Med.25 (2019) 17–24.Search in Google Scholar

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, Oncotarget8 (2017) 83207–83224; https://doi.org/10.18632/oncotarget.2054410.18632/oncotarget.20544566996129137335Search in Google Scholar

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.2017.06.01910.1016/j.ejphar.2017.06.019554268628625568Search in Google Scholar

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 vivo, Nutrients11 (2019) 412; https://doi.org/10.3390/nu1102041210.3390/nu11020412641272430781364Search in Google Scholar

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/ijms1303329110.3390/ijms13033291331771422489153Search in Google Scholar

51. D. Boskou, Olive Oil: Chemistry and Technology, 2^nd ed., AOCS Publishing., Champaign 2006; https://doi.org/10.1201/978143983202810.1201/9781439832028Search in Google Scholar

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/10.1080/1040839070185622310.1080/1040839070185622319093267Search in Google Scholar

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, Molecules12 (2007) 1679-1719.Search in Google Scholar

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.Search in Google Scholar

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/ijms1706084310.3390/ijms17060843492637727258251Search in Google Scholar

56. H. Shamshoum, F. Vlavcheski and E. Tsiani, Anticancer effects of oleuropein, BioFactors43 (2017) 517–528; https://doi.org/10.1002/biof.136610.1002/biof.136628612982Search in Google Scholar

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/10.1111/1750-3841.1419810.1111/1750-3841.1419829928786Search in Google Scholar

58. A. M. Borzì, A. Biondi, F. Basile, S. Luca, E. S. D. Vicari and M. Vacante, Olive oil effects on colorectal cancer, Nutrients11 (2019) 32; https://doi.org/10.3390/nu1101003210.3390/nu11010032635706730583613Search in Google Scholar

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.2014.10.01310.1016/j.jnutbio.2014.10.01325533906Search in Google Scholar

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.2012.13.9.455510.7314/APJCP.2012.13.9.455523167379Search in Google Scholar

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. Cancer117 (2005) 1–7; https://doi.org/10.1002/ijc.2108310.1002/ijc.2108315880398Search in Google Scholar

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.2010.03.00310.1016/j.clnu.2010.03.00320427102Search in Google Scholar

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 1,2-dimethylhydrazine-induced colon carcinogenesis in rats, Eur. J. Nutr.47 (2008) 329–334; https://doi.org/10.1007/s00394-008-0731-x10.1007/s00394-008-0731-x18677543Search in Google Scholar

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. Cancer66 (2014) 1228–1236; https://doi.org/10.1080/01635581.2014.95172710.1080/01635581.2014.95172725207387Search in Google Scholar

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. Cancer66 (2014) 946–954; https://doi.org/10.1080/01635581.2014.92220410.1080/01635581.2014.92220424918476Search in Google Scholar

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 Vitro52 (2018) 243–250; https://doi.org/10.1016/j.tiv.2018.06.02110.1016/j.tiv.2018.06.02129959992Search in Google Scholar

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.6b0493310.1021/acs.jafc.6b0493328071050Search in Google Scholar

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/s00394-011-0230-310.1007/s00394-011-0230-321805082Search in Google Scholar

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/C4FO00187G10.1039/C4FO00187G24953710Search in Google Scholar

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/C5FO00932D10.1039/C5FO00932D26469183Search in Google Scholar

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.20150049810.1002/mnfr.20150049826577496Search in Google Scholar

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.2014.01.02810.1016/j.canlet.2014.01.02824486741Search in Google Scholar

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.2013.285310.3892/or.2013.285324247752Search in Google Scholar

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.20090011110.1002/mnfr.20090011120013881Search in Google Scholar

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.20130032310.1002/mnfr.20130032324019118Search in Google Scholar

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/ijms1907193710.3390/ijms19071937607389030004416Search in Google Scholar

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/s40618-016-0537-210.1007/s40618-016-0537-227592355Search in Google Scholar

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, Biomedicines6 (2018) 11; https://doi.org/10.3390/biomedicines601001110.3390/biomedicines6010011587466829373553Search in Google Scholar

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.2012.12.00910.1016/j.fct.2012.12.00923261678Search in Google Scholar

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.2773810.1002/jcb.2773830260018Search in Google Scholar

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. Foods8 (2014) 269–273; https://doi.org/10.1016/j.jff.2014.03.02710.1016/j.jff.2014.03.027Search in Google Scholar

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. Cancer65 (2013) 147–156; https://doi.org/10.1080/01635581.2013.74175810.1080/01635581.2013.74175823368925Search in Google Scholar

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.2015.326610.3892/mmr.2015.326625634350Search in Google Scholar

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.14012FP10.1254/jphs.14012FP25048019Search in Google Scholar

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.2012.142810.3892/ijo.2012.142822484302Search in Google Scholar

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, Gene585 (2016) 93–99; https://doi.org/10.1016/j.gene.2016.03.03810.1016/j.gene.2016.03.03827032461Search in Google Scholar

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.2017.08.00210.1016/j.jtemb.2017.08.00228965580Search in Google Scholar

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.109.10499210.3945/jn.109.10499219776181Search in Google Scholar

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.2017.09.07210.1016/j.biopha.2017.09.07228946190Search in Google Scholar

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.2782710.1002/jcb.2782730324629Search in Google Scholar

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/ijms15071232310.3390/ijms150712323413984625019344Search in Google Scholar

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, Carcinogenesis32 (2011) 545–553; https://doi.org/10.1093/carcin/bgr00110.1093/carcin/bgr00121216846Search in Google Scholar

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 ONE9 (2014) e97622; https://doi.org/10.1371/journal.pone.009762210.1371/journal.pone.0097622402974024849787Search in Google Scholar

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-0030-127072410.1055/s-0030-127072421328179Search in Google Scholar

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.2018.10.01010.1016/j.bbamcr.2018.10.01030321616Search in Google Scholar

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. Cancer68 (2016) 873–877; https://doi.org/10.1080/01635581.2016.118040710.1080/01635581.2016.118040727266366Search in Google Scholar

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.2016.527010.3892/or.2016.527027878290Search in Google Scholar

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, Oncotarget7 (2016) 43475–43491; https://doi.org/10.18632/oncotarget.978210.18632/oncotarget.9782519003827259268Search in Google Scholar

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.2017.404910.3892/ijo.2017.404928656311Search in Google Scholar

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/10.2174/092986731132019000610.2174/092986731132019000623521677Search in Google Scholar

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/jf400796p10.1021/jf400796p23638972Search in Google Scholar

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.5b0066910.1021/acs.jmedchem.5b0066926225717Search in Google Scholar

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.6b0545710.1021/acs.jafc.6b0545728285526Search in Google Scholar

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-12-024110.1530/JME-12-024123718964Search in Google Scholar

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.2011.02.02510.1016/j.foodchem.2011.02.025Search in Google Scholar

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.2012.12.05010.1016/j.bmc.2012.12.05023403296Search in Google Scholar

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, Oncotarget7 (2016) 32247–32273; https://doi.org/10.18632/oncotarget.868110.18632/oncotarget.8681507801127086914Search in Google Scholar

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.608710.1002/ptr.608729672977Search in Google Scholar

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/jf201459u10.1021/jf201459uSearch in Google Scholar

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) 115-121.10.1002/(SICI)1096-9098(199702)64:2<115::AID-JSO5>3.0.CO;2-ESearch in Google Scholar

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;2-410.1002/(SICI)1097-0215(19960315)65:6<852::AID-IJC24>3.0.CO;2-4Search in Google Scholar

112. L. Kelland, The resurgence of platinum-based cancer chemotherapy, Nat. Rev. Cancer7 (2007) 573–584; https://doi.org/10.1038/nrc216710.1038/nrc2167Search in Google Scholar

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.Search in Google Scholar

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/10.1080/10286020.2017.131775110.1080/10286020.2017.1317751Search in Google Scholar

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_1610.4103/jcrt.JCRT_1040_16Search in Google Scholar

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.839410.1002/rcm.8394Search in Google Scholar

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.1323410.21873/anticanres.13234Search in Google Scholar

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, Molecules23 (2018) 2787; https://doi.org/10.3390/molecules2311278710.3390/molecules23112787Search in Google Scholar

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. Pharmaceutics10 (2013) 3459–3474; https://doi.org/10.1021/mp400311j10.1021/mp400311jSearch in Google Scholar