- Title
- Extraction and utilization of olive waste biophenols; antioxidant and anti-pancreatic cancer activity
- Creator
- Goldsmith, Chloe
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2018
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Olive oil processing leads to thousands of tonnes of waste being produced each year. These waste products (olive pomace and leaf) are usually dumped in landfill; this is causing environmental concerns due to their high concentration of biophenols including oleuropein, hydroxytyrosol, luteolin and apigenin. However, these compounds have known health benefits such as anti-atherogenic, anti-inflammatory as well as anti-cancer properties. Therefore, the extraction and utilization of these biophenols constitutes a viable use for olive waste products while simultaneously reducing the environmental impact of olive processing. Additionally, the anti-cancer potential of olive biophenols has been previously described in vitro for cancers of the breast, colon and prostate. However, there has not yet been any investigation into the activity of olive biophenols in pancreatic cancer. Therefore, the objectives of the present study were: to optimize the aqueous extraction of biophenols from olive waste products, to determine if the aqueous olive waste extracts were a source of major olive biophenols and to assess the anti-pancreatic cancer potential of olive waste extracts and major olive waste biophenols. Water extracts and methanol extracts were prepared from olive leaf and olive pomace waste. All extracts contained a high concentration of phenolic compounds with high antioxidant capacity. The olive leaf extracts (water extract and methanol extract) both contained high concentrations of the major biophenol oleuropein, however, only the methanol extract contained luteolin or apigenin. Additionally, oleuropein was identified in the methanol pomace extract but not in the water extract. Crude olive leaf and pomace extracts displayed anti-cancer activity. Treatment with all extracts (0-200 µg/mL) dose-dependently reduced the proliferation of pancreatic cancer cells (MIA PaCa-2, BxPC-3, CFPAC-1), while a protective effect was observed in non-tumorigenic (HPDE) cells at low doses (50 µg/mL). Furthermore, pure olive waste biophenols displayed selective toxicity. Oleuropein and hydroxytyrosol reduced proliferation, induced cell cycle arrest and induced apoptosis in MIA PaCa-2 cells by increasing the Bax/Bcl-2 ratio and subsequent activation of caspase 3/7. Gene expression analysis suggested that JUN and FOS are involved in oleuropein and hydroxytyrosol induced apoptosis. Additionally, oleuropein exhibited an apparent protective effect on HPDE cells by a decrease in the Bax/Bcl-2 ratio and decrease in expression of ADAMTS-1. Luteolin and apigenin caused cell cycle arrest at G2 and increased expression of caspase 3/7 inducing apoptosis in a number of different pancreatic cancer cell lines (BxPC-3, CFPAC-1, MIA PaCa-2 and ASPC-1); however, toxicity to HPDE cells was higher than cancer cells. In conclusion, water is an effective extraction solvent for the recovery of certain biophenols from olive leaves; however, organic solvents are more suitable for the extraction of major biophenols from pomace waste. Crude olive waste extracts as well as major biophenols displayed selective toxicity towards pancreatic cancer cells while displaying limited toxicity/ a protective effect towards non-tumorigenic pancreas cells. These data highlight the potential of olive biophenols as anti-pancreatic cancer agents, which, warrant further investigation in other models of pancreatic cancer.
- Subject
- olive; pomace; pancreatic cancer; waste utilisation; phenolic compounds; olive leaves; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1383724
- Identifier
- uon:31978
- Rights
- Copyright 2018 Chloe Goldsmith
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 19 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 632 KB | Adobe Acrobat PDF | View Details Download |