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Int J Mol Sci. 2018 Jul 2;19(7). pii: E1937. doi: 10.3390/ijms19071937.

The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells.

Author information

1
Pancreatic Cancer Research Group, School of Environmental & Life Sciences, University of Newcastle, Ourimbah 2258, NSW, Australia. chloe.d.goldsmith@uon.edu.au.
2
Faculty of Science, The University of Newcastle, Ourimbah 2258, NSW, Australia. chloe.d.goldsmith@uon.edu.au.
3
Pancreatic Cancer Research Group, School of Environmental & Life Sciences, University of Newcastle, Ourimbah 2258, NSW, Australia. Danielle.Bond@newcastle.edu.au.
4
Faculty of Health, The University of Newcastle, Ourimbah 2258, NSW, Australia. Danielle.Bond@newcastle.edu.au.
5
Hunter Medical Research Institute (HMRI), New Lambton Heights 2305, NSW, Australia. Danielle.Bond@newcastle.edu.au.
6
Faculty of Health, The University of Newcastle, Ourimbah 2258, NSW, Australia. Helen.Jankowski@uon.edu.au.
7
Hunter Medical Research Institute (HMRI), New Lambton Heights 2305, NSW, Australia. Helen.Jankowski@uon.edu.au.
8
Faculty of Health, The University of Newcastle, Ourimbah 2258, NSW, Australia. Judith.Weidenhofer@newcastle.edu.au.
9
Hunter Medical Research Institute (HMRI), New Lambton Heights 2305, NSW, Australia. Judith.Weidenhofer@newcastle.edu.au.
10
School of Science, Engineering and Technology, University of Abertay, Dundee, Scotland DD1 1HG, UK. c.stathopoulos@abertay.ac.uk.
11
Faculty of Science, The University of Newcastle, Ourimbah 2258, NSW, Australia. Paul.Roach@newcastle.edu.au.
12
Pancreatic Cancer Research Group, School of Environmental & Life Sciences, University of Newcastle, Ourimbah 2258, NSW, Australia. C.Scarlett@newcastle.edu.au.
13
Faculty of Science, The University of Newcastle, Ourimbah 2258, NSW, Australia. C.Scarlett@newcastle.edu.au.
14
Hunter Medical Research Institute (HMRI), New Lambton Heights 2305, NSW, Australia. C.Scarlett@newcastle.edu.au.

Abstract

Current chemotherapy drugs for pancreatic cancer only offer an increase in survival of up to six months. Additionally, they are highly toxic to normal tissues, drastically affecting the quality of life of patients. Therefore, the search for novel agents, which induce apoptosis in cancer cells while displaying limited toxicity towards normal cells, is paramount. The olive biophenols, oleuropein, hydroxytyrosol and tyrosol, have displayed cytotoxicity towards cancer cells without affecting non-tumorigenic cells in cancers of the breast and prostate. However, their activity in pancreatic cancer has not been investigated. Therefore, the aim of this study was to determine the anti-pancreatic cancer potential of oleuropein, hydroxytyrosol and tyrosol. Pancreatic cancer cells (MIA PaCa-2, BxPC-3, and CFPAC-1) and non-tumorigenic pancreas cells (HPDE) were treated with oleuropein, hydroxytyrosol and tyrosol to determine their effect on cell viability. Oleuropein displayed selective toxicity towards MIA PaCa-2 cells and hydroxytyrosol towards MIA PaCa-2 and HPDE cells. Subsequent analysis of Bcl-2 family proteins and caspase 3/7 activation determined that oleuropein and hydroxytyrosol induced apoptosis in MIA PaCa-2 cells, while oleuropein displayed a protective effect on HPDE cells. Gene expression analysis revealed putative mechanisms of action, which suggested that c-Jun and c-Fos are involved in oleuropein and hydroxytyrosol induced apoptosis of MIA PaCa-2 cells.

KEYWORDS:

HPDE; MIA PaCa-2; anti-cancer; chemoprevention; hydroxytyrosol; nutraceutical; oleuropein; olive; phenolic compound

PMID:
30004416
PMCID:
PMC6073890
DOI:
10.3390/ijms19071937
[Indexed for MEDLINE]
Free PMC Article

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