The Effect of Oil Palm Phenolics (OPP) on Pancreatic Ductal Adenocarcinoma (PDAC) in Transgenic Mouse Model

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive form of pancreatic cancer with low survival rates partly due to late diagnosis and poor treatment outcomes. The potential curative treatment through surgical resection is only limited to early stages of PDAC while the use of chemotherapy drug, gemcitabine alone offers minimal benefits. This study aimed to explore the in vivo effects of oil palm phenolics (OPP), a water‐soluble extract from African oil palm, Elaeis guineensis, in transgenic mouse model of PDAC.MethodsSix‐week dietary treatment was carried out on KPC (k‐ras and p53 conditional mutant) mice divided into four groups: KC (control diet), KP (5% OPP diet), KG (gemcitabine), KPG (5% OPP diet + gemcitabine). Littermates without mutations served as controls: CC (control diet) and CP (5% OPP diet). Progression of PDAC was monitored with MRI at weeks 1 and 5 of the study. Histological analysis was performed on fore stomach and pancreatic tissue slides stained with hematoxylin and eosin (H&E) for toxicity study and PDAC staging respectively. Imunnohistochemistry with S100 Calcium Binding Protein P (S100P) and SMAD4/DPC4 proteins were used to validate the histological changes seen with H&E staining. Change in gene expression on pancreatic tissue was evaluated by real time real‐time polymerase chain reaction.ResultsFore stomach histological analyses showed that dietary OPP did not exhibit sign of toxicity in control group (CP). OPP treated groups (KP and KPG) had a slower progression of tumor and compared to KC and KG as seen by changes in tumor volumes observed with MRI. All treatment groups (KG, KP and KPG) had a significant decrease in total number of Pancreatic Intraepithelial Neoplasia (PanIN) where the combination of OPP and gemcitabine (KPG) displayed the lowest count. Compared to the KC group, expression of matrix metallopeptidase 9 (MMP9), cyclin D1 (CCND1), and notch homolog 1 (Notch1) genes was down regulated most significantly in KPG group. Collectively, the results demonstrate potential benefit of dietary OPP as part of combinatorial therapy against progression of PDAC.Support or Funding InformationThis study was funded by Malaysian Palm Oil Board (MPOB).