AIM OF THE STUDY: The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death.

MATERIALS AND METHODS: MDA-MB-231 cells were incubated with PMEAF for 24h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array.

RESULTS: The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G0/G1 and G2/M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆Ψm) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells.

METHODS: Female Sprague-Dawley rats were allocated into four groups (n = 8) as follows: (i) the Normal Control group (NC), (ii) the BPA-exposed group (PC), (iii) the group concurrently treated with BPA and F. deltoidea (FC) and (iv) the group treated with F. deltoidea alone (F).

RESULTS: After 6 weeks of concurrent treatment with F. deltoidea, uterine abnormalities in the BPA-exposed rats showed a significant improvement. Specifically, the size of stromal cells increased; interstitial spaces between stromal cells expanded; the histology of the glandular epithelium and the myometrium appeared normal and mitotic figures were present. The suppressive effects of BPA on the expression levels of sex steroid receptors (ERα and ERβ) and the immunity gene C3 were significantly normalised by F. deltoidea treatment. The role of F. deltoidea as an antioxidant agent was proven by the significant reduction in malondialdehyde level in BPA-exposed rats. Moreover, in BPA-exposed rats, concurrent treatment with F. deltoidea could normalise the level of the gonadotropin hormone, which could be associated with an increase in the percentage of rats with a normal oestrous cycle.

PURPOSE: In this study, we aimed to discover the role of oil palm phenolics (OPP) in influencing the gene expression changes caused by an atherogenic diet in mice.

METHODS: We fed mice with either a low-fat normal diet (14.6 % kcal/kcal fat) with distilled water, or a high-fat atherogenic diet (40.5 % kcal/kcal fat) containing cholesterol. The latter group was given either distilled water or OPP. We harvested major organs such as livers, spleens and hearts for microarray gene expression profiling analysis. We determined how OPP changed the gene expression profiles caused by the atherogenic diet. In addition to gene expression studies, we carried out physiological observations, blood hematology as well as clinical biochemistry, cytokine profiling and antioxidant assays on their blood sera.

RESULTS: Using Illumina microarrays, we found that the atherogenic diet caused oxidative stress, inflammation and increased turnover of metabolites and cells in the liver, spleen and heart. In contrast, OPP showed signs of attenuating these effects. The extract increased unfolded protein response in the liver, attenuated antigen presentation and processing in the spleen and up-regulated antioxidant genes in the heart. Real-time quantitative reverse transcription-polymerase chain reaction validated the microarray gene expression fold changes observed. Serum cytokine profiling showed that OPP attenuated inflammation by modulating the Th1/Th2 axis toward the latter. OPP also increased serum antioxidant activity to normal levels.