Abstract
Background: Pancreatic cancer is a devastating disease with a 5-year survival rate of less than 5%. The heterogeneity of the disease, resistance to conventional treatment options and toxicity of current chemotherapy agents (FOLFIRINOX, gemcitabine) makes pancreatic cancer an important target for the development of novel therapeutic agents. Individual compounds isolated from olive products have been investigated extensively for their anticancer activity in cancers of the breast, colon, prostate and leukemia, however there is limited research into their effects against pancreatic cancer.
Aims: This study aimed to assess the antipancreatic cancer potential of individual olive phenolic compounds.
Methods: Pancreatic cancer (BxPC-3, CFPAC-1, MiaPaCa-2), and normal human pancreatic ductal epithelial (HPDE) cells were treated with oleuropein, hydroxytyrosol, myrictin, luteolin and apigenin. Cell viability was assessed using the CCK-8 viability assay. The induction of apoptosis was assessed by way of caspase 3/7 activation and cell-cycle analysis was performed using a MUSE flow cell analyzer.
Results: Most notable results include the IC50 values for luteolin and apigenin on BxPC-3 cells (10 and 12 μM, respectively) and CFPAC-1 cells (22 and 25 μM, respectively). Apigenin also induced G2-phase arrest in both CFPAC-1 and BxPC-3 cells. Interestingly, MiaPaCa-2 pancreatic cancer cells treated with a high dose of oleuropein (200 μM) resulted in viability of 4%, whereas no effect was observed for the normal pancreas (HPDE) cells at this concentration. After treatment of MiaPaCa-2 cells with 100 μM of oleuropein, a significant induction of apoptosis, as measured by increased activation of caspase 3/7, was observed.
Conclusions: Olive phenolic compounds demonstrate selective toxicity toward different pancreatic cancer cell lines, with oleuropein displaying no toxicity to normal pancreatic cells and, therefore, warrant further investigation.
Translational research aspect: This study aligns with the T1 translational pipeline in that is assessing the in vitro potential of novel chemotherapeutic agents for pancreatic cancer.