Evening Primrose Oil effects in human Pancreatic Ductal Adenocarcinoma cell lines

Evening Primrose (Oenothera L.) is a medicinal plant and the most numerous species in the Oenothera L. family is the Oenothera biennis. Evening Primrose Oil (EPO), obtained from its seeds, is rich in triacylglycerols and the main ones are linoleic acid (LA) (70–74%) and γ-linolenic acid (GLA) (8–10%), polyunsaturated fatty acids (PUFAs), belonging to omega-6 acids group [1]. The presence of GLA makes EPO a valid dietary supplement to reduce triacyclglycerols and low-density lipoprotein (LDL) in plasma and an interesting compound for the treatment of rheumatic and arthritic conditions and for atopic dermatitis [1,2]. LA and GLA are precursors of dihomo-linolenic acid (DGLA), that is metabolized in series 1 prostaglandins and is oxidized in 15-hydroxyeicosatrienoic acid (15-HETrE) with anti-inflammatory and anti-proliferative effect, but at the same time, they can be also converted in arachidonic acid (AA), inducing pro-inflammatory series 2 prostaglandins and series 4 leukotrienes [1]. EPO is also composed by unsaponifiable compounds and among these, the sterols have important role in the reduction of pro-inflammatory mediators [2]. Moreover, several studies demonstrated GLA antitumoral activities in different cancer cell types and its ability to enhance chemotherapeutic drugs activity [3]. Pancreatic Ductal Adenocarcinoma (PDAC) is an infiltrating neoplasm with glandular differentiation derived from the pancreatic ductal tree. Among the solid cancers, it is considered one of the most aggressive, with five years survival of 5-7% [4-6]. It was demonstrated a family genetic predisposition, but also some precursor lesions within pancreatic tissue and somatic mutations of KRAS oncogene and CDKN2A, TP53 and SMAD4 suppressor genes are implicated in PDAC pathogenesis [4,7,8]. In the last years scientific interest in using molecules of natural origins as adjuvant in cancer therapy is grown [9]. Several phytochemicals demonstrated anticancer properties, thanks to their effects in suppressing cancer cell survival and proliferation, in inducing cancer cell death and for their synergistic/adjuvant interactions with different molecular pathways targets of chemotherapeutical drugs. [10]. Particularly, a study evidenced a reduction of pancreatic cancer cells growth, migration and invasion by treatment with DGLA [11]. So, since LA and GLA are the most important triacyclglycerols present in EPO, we decided to analyze the effects of EPO in two human pancreatic ductal adenocarcinoma cell lines (PANC-1 and MIAPaCa-2). Data showed a reduction of cancer cell vitality after administration of EPO and an induction of cancer cell death as confirmed by Western Blot analysis. Then, the effects of EPO were also evaluated on its ability to modulate the main pathways involved in PDAC aggressiveness. In conclusion, these preliminary data suggest a potential role of EPO in PDAC aggressiveness.