Abstract
Pancreatic cancer is a devastating disease with a 5-year survival rate of less than 5%. Resistance to conventional treatment options and toxicity of current chemotherapy agents (gemcitabine) makes pancreatic cancer a target for the development of novel therapeutic agents. Oleuropein is the most abundant biophenol found in olive products; it has anti-atherogenic and anti-inflammatory properties as well as activity against cancers of the breast, colon and prostate. However, there has yet to be any investigation into the effects of oleuropein on pancreatic cancer cells. Consequently, this study aimed to assess the anti-pancreatic cancer activity of oleuropein in vitro. Two cell lines were investigated; a pancreatic cancer cell line (MiaPaCa-2) and a normal pancreas cell line (HPDE). The viability of cells after treatment with 0-200μM oleuropein was assessed using the Dojindo CCK-8 viability assay and compared to gemcitabine. The induction of apoptosis was measured by way of caspase 3/7 activation, using a MUSE flow cell analyser, and expression of Bcl-2, Bax and Bac using Western blot. Cell cycle analysis was conducted using the MUSE flow cell analyser. RNA expression was assessed using Affymetrix GeneChip® Whole Transcript (WT) expression arrays. The IC50 values for oleuropein against MiaPaCa-2 cells was148μM. However, importantly, oleuropein did not decrease the viability of HPDE cells within the treatment range. In comparision, 20nM of gemcitabine did not show selectivity; it reduced the viability of MiaPaCa-2 cells to 21% and of HPDE cells to 2%. An increase in the expression of caspase 3/7 was seen in MiaPaCa-2 cells when treated with oleuropein but it had no effect on the HPDE cells. Furthermore, when treated with oleuropein, an increase in the expression of genes involved in the NRF-2 (oxidative stress) pathway was observed in MiaPaCa-2 cells, an effect not observed in HPDE cells.
Conclusion Oleuropein selectively induced apoptosis in the pancreatic cancer cells (MiaPaCa-2), appearing non-toxic to normal pancreas cells (HPDE) within the treatment ranges; this is significant, since gemcitabine was comparatively more toxic to HPDE cells. Furthermore, the link between oleuropein and the NRF-2 pathway in MiaPaCa-2 cells justifies further study into the mechanisms of action of oleuropein and its potential as a novel therapeutic approach for pancreatic cancer.
Note: This abstract was not presented at the meeting.