Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion of MDA-MB-231 Triple-Negative Breast Cancer Cell via Induction of Autophagy

Author(s): Hui-Yuan Lu*, Jian-Sheng Zhu, Zhan Zhang, Wei-Jian Shen, Shan Jiang, Yun-Feng Long, Bin Wu, Tao Ding, Fei Huan and Shou-Lin Wang

Volume 19, Issue 16, 2019

Page: [1983 - 1990] Pages: 8

DOI: 10.2174/1871520619666190722101207

Price: $65

Abstract

Background: Breast Cancer (BC) is the leading cause of cancer-related deaths among women. As such, novel chemotherapeutic agents are urgently needed, especially for Triple-Negative Breast Cancer (TNBC). Hydroxytyrosol (HT) and Oleuropein (OL) are rich in olive oil, which is associated with a low occurrence of BC. However, the effects and mechanisms of action of HT and OL in BC cells are still unclear. This study aimed to explore the molecular mechanisms underlying the antitumor effect of HT and OL in TNBC.

Methods: TNBC MDA-MB-231 cells were treated with HT and OL in combination with Hepatocyte Growth Factor (HGF), rapamycin (Rapa, an inducer of autophagy) or 3-methyladenine (3-MA, an inhibitor of autophagy). Cell viability, migration, invasion, and autophagy signaling were analyzed by scratch assays, transwell migration assays, and Western blot analysis.

Results: Treatment with HT or OL reduced MDA-MB-231 cell viability in a dose-dependent manner. MDAMB- 231 cells were more sensitive to HT treatment than OL treatment. Rapa treatment could significantly block HGF-induced MDA-MB-231 cell migration and invasion, suggesting that inhibition of autophagy could promote migration and invasion. Moreover, HT or OL treatment significantly suppressed HGF or 3-MA induced cell migration and invasion by reversing LC3-II/LC3-I and Beclin-1 downregulation and reversing p62 upregulation.

Conclusion: These data indicated that HT and OL may inhibit migration and invasion of TNBC cells by activating autophagy. These findings provide potential therapeutic strategies that target autophagy to limit the pathogenesis and progression of BC.

Keywords: Autophagy, hydroxytyrosol, MDA-MB-231, oleuropein, triple-negative breast cancer, hepatocyte growth factor.

« Previous Next »
Graphical Abstract

[1]
Spronk, I.; Schellevis, F.G.; Burgers, J.S.; de Bock, G.H.; Korevaar, J.C. Incidence of isolated local breast cancer recurrence and contralateral breast cancer: A systematic review. Breast, 2018, 39, 70-79.
[http://dx.doi.org/10.1016/j.breast.2018.03.011] [PMID: 29621695]
[2]
Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[3]
Dent, R.; Trudeau, M.; Pritchard, K.I.; Hanna, W.M.; Kahn, H.K.; Sawka, C.A.; Lickley, L.A.; Rawlinson, E.; Sun, P.; Narod, S.A. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin. Cancer Res., 2007, 13(15 Pt 1), 4429-4434.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-3045] [PMID: 17671126]
[4]
Sharma, P. Update on the treatment of early-stage triple-negative breast cancer. Curr. Treat. Options Oncol., 2018, 19(5), 22.
[http://dx.doi.org/10.1007/s11864-018-0539-8] [PMID: 29656345]
[5]
Malorni, L.; Shetty, P.B.; De Angelis, C.; Hilsenbeck, S.; Rimawi, M.F.; Elledge, R.; Osborne, C.K.; De Placido, S.; Arpino, G. Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up. Breast Cancer Res. Treat., 2012, 136(3), 795-804.
[http://dx.doi.org/10.1007/s10549-012-2315-y] [PMID: 23124476]
[6]
Han, J.; Talorete, T.P.; Yamada, P.; Isoda, H. Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells. Cytotechnology, 2009, 59(1), 45-53.
[http://dx.doi.org/10.1007/s10616-009-9191-2] [PMID: 19353300]
[7]
Hong, W.K. General keynote: The impact of cancer chemoprevention. Gynecol. Oncol., 2003, 88(1 Pt 2), S56-S58.
[http://dx.doi.org/10.1006/gyno.2002.6685] [PMID: 12586087]
[8]
Owen, R.W.; Giacosa, A.; Hull, W.E.; Haubner, R.; Würtele, G.; Spiegelhalder, B.; Bartsch, H. Olive-oil consumption and health: The possible role of antioxidants. Lancet Oncol., 2000, 1, 107-112.
[http://dx.doi.org/10.1016/S1470-2045(00)00015-2] [PMID: 11905662]
[9]
Samara, P.; Christoforidou, N.; Lemus, C.; Argyropoulou, A.; Ioannou, K.; Vougogiannopoulou, K.; Aligiannis, N.; Paronis, E.; Gaboriaud-Kolar, N.; Tsitsilonis, O.; Skaltsounis, A.L. New semi-synthetic analogs of oleuropein show improved anticancer activity in vitro and in vivo. Eur. J. Med. Chem., 2017, 137, 11-29.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.029] [PMID: 28551177]
[10]
Li, S.; Han, Z.; Ma, Y.; Song, R.; Pei, T.; Zheng, T.; Wang, J.; Xu, D.; Fang, X.; Jiang, H.; Liu, L. Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: An in vivo and in vitro study. Oncol. Rep., 2014, 31(1), 145-152.
[http://dx.doi.org/10.3892/or.2013.2853] [PMID: 24247752]
[11]
Sirianni, R.; Chimento, A.; De Luca, A.; Casaburi, I.; Rizza, P.; Onofrio, A.; Iacopetta, D.; Puoci, F.; Andò, S.; Maggiolini, M.; Pezzi, V. Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation. Mol. Nutr. Food Res., 2010, 54(6), 833-840.
[http://dx.doi.org/10.1002/mnfr.200900111] [PMID: 20013881]
[12]
Choupani, J.; Alivand, M.R.; Derakhshan, M.S.; Zaeifizadeh, M.; Khaniani, S.M. Oleuropein inhibits migration ability through suppression of epithelial-mesenchymal transition and synergistically enhances doxorubicin-mediated apoptosis in MCF-7 cells. J. Cell. Physiol., 2019, 234(6), 9093-9104.
[13]
Tan, Y.Q.; Zhang, J.; Zhou, G. Autophagy and its implication in human oral diseases. Autophagy, 2017, 13(2), 225-236.
[http://dx.doi.org/10.1080/15548627.2016.1234563] [PMID: 27764582]
[14]
Lu, J.; Dong, W.; He, H.; Han, Z.; Zhuo, Y.; Mo, R.; Liang, Y.; Zhu, J.; Li, R.; Qu, H.; Zhang, L.; Wang, S.; Ma, R.; Jia, Z.; Zhong, W. Autophagy induced by overexpression of DCTPP1 promotes tumor progression and predicts poor clinical outcome in prostate cancer., Int. J. Biol. Macromol., 2018, 118(Pt A), 599-609.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.06.005]
[15]
Soto-Alarcon, S.A.; Valenzuela, R.; Valenzuela, A.; Videla, L.A. Liver protective effects of extra virgin olive oil: Interaction between its chemical composition and the cell-signaling pathways involved in protection. Endocr. Metab. Immune Disord. Drug Targets, 2018, 18(1), 75-84.
[PMID: 29141573]
[16]
Pantano, D.; Luccarini, I.; Nardiello, P.; Servili, M.; Stefani, M.; Casamenti, F. Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology. Br. J. Clin. Pharmacol., 2017, 83(1), 54-62.
[http://dx.doi.org/10.1111/bcp.12993] [PMID: 27131215]
[17]
Luo, C.; Li, Y.; Wang, H.; Cui, Y.; Feng, Z.; Li, H.; Li, Y.; Wang, Y.; Wurtz, K.; Weber, P.; Long, J.; Liu, J. Hydroxytyrosol promotes superoxide production and defects in autophagy leading to anti-proliferation and apoptosis on human prostate cancer cells. Curr. Cancer Drug Targets, 2013, 13(6), 625-639.
[http://dx.doi.org/10.2174/15680096113139990035] [PMID: 23597197]
[18]
Zhang, Z.; Lu, H.; Huan, F.; Meghan, C.; Yang, X.; Wang, Y.; Wang, X.; Wang, X.; Wang, S.L. Cytochrome P450 2A13 mediates the neoplastic transformation of human bronchial epithelial cells at a low concentration of aflatoxin B1. Int. J. Cancer, 2014, 134(7), 1539-1548.
[http://dx.doi.org/10.1002/ijc.28489] [PMID: 24114584]
[19]
Kim, K.H.; Kim, J.Y.; Kwak, J.H.; Pyo, S. Different anticancer effects of Saxifragifolin A on estrogen receptor-positive and estrogen receptor-negative breast cancer cells. Phytomedicine, 2015, 22(9), 820-828.
[http://dx.doi.org/10.1016/j.phymed.2015.05.057] [PMID: 26220629]
[20]
Agarwal, G.; Nanda, G.; Lal, P.; Mishra, A.; Agarwal, A.; Agrawal, V.; Krishnani, N. Outcomes of Triple-Negative Breast Cancers (TNBC) compared with non-TNBC: Does the survival vary for all stages? World J. Surg., 2016, 40(6), 1362-1372.
[http://dx.doi.org/10.1007/s00268-016-3422-4] [PMID: 26842691]
[21]
Guo, Y.; Pei, X. Tetrandrine-induced autophagy in MDA-MB-231 triple-negative breast cancer cell through the inhibition of PI3K/AKT/mTOR signaling. Evid. Based Complement. Alternat. Med., 2019, 20197517431
[http://dx.doi.org/10.1155/2019/7517431] [PMID: 30713576]
[22]
Jia, L.; Huang, S.; Yin, X.; Zan, Y.; Guo, Y.; Han, L. Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction. Life Sci., 2018, 208, 123-130.
[http://dx.doi.org/10.1016/j.lfs.2018.07.027] [PMID: 30025823]
[23]
Chen, J.; Zhu, Y.; Zhang, W.; Peng, X.; Zhou, J.; Li, F.; Han, B.; Liu, X.; Ou, Y.; Yu, X. Delphinidin induced protective autophagy via mTOR pathway suppression and AMPK pathway activation in HER-2 positive breast cancer cells. BMC Cancer, 2018, 18(1), 342.
[http://dx.doi.org/10.1186/s12885-018-4231-y] [PMID: 29587684]
[24]
Lv, Q.; Wang, W.; Xue, J.; Hua, F.; Mu, R.; Lin, H.; Yan, J.; Lv, X.; Chen, X.; Hu, Z.W. DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer. Cancer Res., 2012, 72(13), 3238-3250.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3832] [PMID: 22719072]
[25]
Liu, F.; Sang, M.; Meng, L.; Gu, L.; Liu, S.; Li, J.; Geng, C. miR92b promotes autophagy and suppresses viability and invasion in breast cancer by targeting EZH2. Int. J. Oncol., 2018, 53(4), 1505-1515.
[http://dx.doi.org/10.3892/ijo.2018.4486] [PMID: 30066891]
[26]
Harrison, S.M.; Knifley, T.; Chen, M.; O’Connor, K.L. LPA, HGF, and EGF utilize distinct combinations of signaling pathways to promote migration and invasion of MDA-MB-231 breast carcinoma cells. BMC Cancer, 2013, 13, 501.
[http://dx.doi.org/10.1186/1471-2407-13-501] [PMID: 24160245]
[27]
Kuang, W.; Deng, Q.; Deng, C.; Li, W.; Shu, S.; Zhou, M. Hepatocyte growth factor induces breast cancer cell invasion via the PI3K/AKT and p38 MAPK signaling pathways to up-regulate the expression of COX2. Am. J. Transl. Res., 2017, 9(8), 3816-3826.
[PMID: 28861172]
[28]
Vizzotto, M.; Porter, W.; Byrne, D.; Cisneros-Zevallos, L. Polyphenols of selected peach and plum genotypes reduce cell viability and inhibit proliferation of breast cancer cells while not affecting normal cells. Food Chem., 2014, 164, 363-370.
[http://dx.doi.org/10.1016/j.foodchem.2014.05.060] [PMID: 24996346]
[29]
Fernando, W.; Coombs, M.R.P.; Hoskin, D.W.; Rupasinghe, H.P.V. Docosahexaenoic acid-acylated phloridzin, a novel polyphenol fatty acid ester derivative, is cytotoxic to breast cancer cells. Carcinogenesis, 2016, 37(10), 1004-1013.
[http://dx.doi.org/10.1093/carcin/bgw087] [PMID: 27535497]
[30]
Dewangan, J.; Tandon, D.; Srivastava, S.; Verma, A.K.; Yapuri, A.; Rath, S.K. Novel combination of salinomycin and resveratrol synergistically enhances the anti-proliferative and pro-apoptotic effects on human breast cancer cells. Apoptosis, 2017, 22(10), 1246-1259.
[http://dx.doi.org/10.1007/s10495-017-1394-y] [PMID: 28748373]
[31]
Warleta, F.; Quesada, C.S.; Campos, M.; Allouche, Y.; Beltrán, G.; Gaforio, J.J. Hydroxytyrosol protects against oxidative DNA damage in human breast cells. Nutrients, 2011, 3(10), 839-857.
[http://dx.doi.org/10.3390/nu3100839] [PMID: 22254082]
[32]
Elamin, M.H.; Daghestani, M.H.; Omer, S.A.; Elobeid, M.A.; Virk, P.; Al-Olayan, E.M.; Hassan, Z.K.; Mohammed, O.B.; Aboussekhra, A. Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells. Food Chem. Toxicol., 2013, 53, 310-316.
[http://dx.doi.org/10.1016/j.fct.2012.12.009] [PMID: 23261678]
[33]
Hassan, Z.K.; Elamin, M.H.; Omer, S.A.; Daghestani, M.H.; Al-Olayan, E.S.; Elobeid, M.A.; Virk, P. Oleuropein induces apoptosis via the p53 pathway in breast cancer cells. Asian Pac. J. Cancer Prev., 2014, 14(11), 6739-6742.
[http://dx.doi.org/10.7314/APJCP.2013.14.11.6739] [PMID: 24377598]
[34]
Cruz-Lozano, M.; González-González, A.; Marchal, J.A.; Muñoz-Muela, E.; Molina, M.P.; Cara, F.E.; Brown, A.M.; García-Rivas, G.; Hernández-Brenes, C.; Lorente, J.A.; Sanchez-Rovira, P.; Chang, J.C.; Granados-Principal, S. Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways. Eur. J. Nutr., 2019, 58(8), 3207-3219.
[http://dx.doi.org/10.1007/s00394-018-1864-1] [PMID: 30460610]
[35]
Cordero, J.G.; García-Escudero, R.; Avila, J.; Gargini, R.; García-Escudero, V. Benefit of oleuropein aglycone for Alzheimer’s disease by promoting autophagy. Oxid. Med. Cell. Longev., 2018, 20185010741
[http://dx.doi.org/10.1155/2018/5010741] [PMID: 29675133]
[36]
Mosele, J.I.; Martín-Peláez, S.; Macià, A.; Farràs, M.; Valls, R.M.; Catalán, Ú.; Motilva, M.J. Faecal microbial metabolism of olive oil phenolic compounds: In vitro and in vivo approaches. Mol. Nutr. Food Res., 2014, 58(9), 1809-1819.
[http://dx.doi.org/10.1002/mnfr.201400124] [PMID: 24990102]
[37]
Carrasco-Pancorbo, A.; Cerretani, L.; Bendini, A.; Segura-Carretero, A.; Lercker, G.; Fernández-Gutiérrez, A. Evaluation of the influence of thermal oxidation on the phenolic composition and on the antioxidant activity of extra-virgin olive oils. J. Agric. Food Chem., 2007, 55(12), 4771-4780.
[http://dx.doi.org/10.1021/jf070186m] [PMID: 17497881]
[38]
Balducci, V.; Incerpi, S.; Stano, P.; Tofani, D. Antioxidant activity of hydroxytyrosyl esters studied in liposome models. Biochim. Biophys. Acta Biomembr., 2018, 1860(2), 600-610.
[http://dx.doi.org/10.1016/j.bbamem.2017.11.012] [PMID: 29175103]
[39]
Visioli, F.; Poli, A.; Gall, C. Antioxidant and other biological activities of phenols from olives and olive oil. Med. Res. Rev., 2002, 22(1), 65-75.
[http://dx.doi.org/10.1002/med.1028] [PMID: 11746176]
[40]
Goldsmith, C.D.; Bond, D.R.; Jankowski, H.; Weidenhofer, J.; Stathopoulos, C.E.; Roach, P.D.; Scarlett, C.J. The olive biophenols oleuropein and hydroxytyrosol selectively reduce proliferation, influence the cell cycle, and induce apoptosis in pancreatic cancer cells. Int. J. Mol. Sci., 2018, 19(7)E1937
[http://dx.doi.org/10.3390/ijms19071937] [PMID: 30004416]

Rights & Permissions Print Cite
Article Metrics
49
7
© 2024 Bentham Science Publishers | Privacy Policy