No abstract

Increased polyamine concentrations play an important role in the development of cancer at all stages, from initiation through to maintenance of the transformed phenotype. One way cancer cells accumulate increased concentrations of polyamines is by increased uptake of preformed polyamines via their PTS (polyamine transport system). The PTS is promiscuous and will transport a range of polyamine-based molecules. Therefore it may be that cytotoxic drugs could be attached to polyamine vectors and targeted selectively to cancer cells by utilizing the PTS. The aim of the present study was to investigate the potential of Ant 4, a putrescine–anthracene conjugate, to target cytotoxic agents to human cancer cells as a paradigm for a novel method of selective drug delivery. Ant 4 induced cytotoxicity after only 24 h exposure. Apoptosis was the predominant type of cell death, with mechanistic studies revealing that oxidative stress and DNA damage may have a part to play. For the first time, uptake of Ant 4 via the PTS was demonstrated both directly and indirectly in human cell lines. In addition, Ant 4 significantly reduced putrescine uptake, demonstrating that this conjugate not only used the PTS, but also could successfully compete with its native polyamine for uptake. However, the most interesting finding was the intracellular depletion of the polyamine pools, providing an additional mode of toxicity for Ant 4 and the possibility that this molecule may act as a ‘double-edged sword’: preventing cell growth by delivery of the toxic moiety and by depletion of intracellular polyamine content.

Our results show that B. angulata fruit is beneficial in positively influencing and managing oxidative damage.

Higher doses of B. angulata juice exerted better antioxidant activity.

One of the major problems in cancer therapy is the lack of specificity of chemotherapeutic agents towards cancer cells, resulting in adverse side effects. One means to counter this is to selectively deliver the drug to the cancer cell. Cancer cells accumulate increased concentrations of polyamines compared to normal cells, mainly through an increased uptake of preformed polyamines via the polyamine transport system (PTS). Furthermore, the non-stringent structural requirements of the PTS enable the transport of a range of polyamine-based molecules. Thus, the PTS can be used to transport compounds linked to polyamines selectively to cancer cells. In our laboratory, polyamine-anthracene conjugates have shown potent anti-tumour activity towards HL-60 cells. The aim of this study was to determine the cytotoxicity of Ant-4,4, a homospermidine-anthracene conjugate, and assess the long-term effects by determining whether cancer cells were able to recover from treatment. During exposure, Ant-4,4 was an effective growth-inhibitory agent in HL-60 cells decreasing viable cell number, protein and polyamine content. Evidence indicates concomitant cell-cycle arrest and increased apoptosis. Once the drug was removed, HL-60 cells recovered gradually over time. Increasing cell number, protein content and polyamine content, as well as diminished effects on cell-cycle and apoptotic stimuli were observed over time. These data suggest that, despite being an effective way of delivering anthracene, these polyamine conjugates do not exert long-lasting effects on HL-60 cells.

Purpose Cardiovascular disease (CVD) is the leading and the most critical type of chronic disease. Atherosclerosis is the most common cause of CVD. Inflammation has been progressively acknowledged as a vital and central player in the pathophysiology of atherosclerosis. Baccaurea angulata is an underutilized fruit of the island of Borneo. It was obtained from Bau, Sarawak, Malaysia. In our previous studies, B. angulata did not only increase antioxidant enzyme activities, but also slowed the lipid peroxidation process in high-cholesterol-fed rabbits. It was hypothesized that B. angulata fruit would exert an anti-inflammatory effect. This study, therefore, aimed at evaluating and comparing the effects of three different B. angulata whole fruit (WF) juice doses on 11 serum inflammatory biomarkers of atherosclerosis. Methods Thirty-five male New Zealand white rabbits were divided into seven groups (n=5). Group CH was fed 1% cholesterol diet only, group C1 was fed 1% cholesterol diet and 0.5 ml/kg/day B. angulata WF juice, group C2 was fed 1% cholesterol diet and 1.0 ml/kg/day B. angulata WF juice, group C3 was fed 1% cholesterol diet and 1.5 ml/kg/day B. angulata WF juice, group N was fed standard pellet only, group N1 was fed standard pellet and 0.5 ml/kg/day B. angulata WF juice, and group N2 was fed standard pellet and 1.0 ml/kg/day B. angulata WF juice for 12 weeks. Results The administration of the various juices reduced the concentrations of induced serum inflammatory biomarkers. Conclusion This protective effect of B. angulata fruit against cardiovascular risk might be due to its polyphenol content.

Introduction: This study aimed to determine the relationship of maternal dietary intake with human milk nutritional composition, among Malay mothers during the postpartum period of exclusive breastfeeding. Methods: Human milk samples (20-30ml) were collected from mothers (n=32) at least once monthly for six months postpartum. Macronutrients and fatty acids contents were determined using proximate analysis and gas chromatography methods, respectively. Maternal dietary intakes were recorded using the multiple-pass diet recall method prior to each milk sampling and were analysed using the Nutritionist Pro TM software. Associations between the milk composition and maternal diet were tested using Spearman correlation. Results: The energy content ranged between 49.6-59.2 kcal/100ml, protein 1.3-1.4 g/100ml, carbohydrate 6.5-9.7 g/100ml and total fat 6.5-9.7 g/100ml. The polyunsaturated, monounsaturated, and saturated fatty acids concentrations were 10.5-19.1 %, 40.6-43.5 %, and 38.0-49.7 %, respectively. During confinement (first month postpartum), total energy and total fat content of human milk were the highest whereas total carbohydrate was the lowest, compared to the rest of the exclusive breastfeeding period. In contrast, intakes of total calorie and total fat were the lowest, whereas protein was the highest during this period. However, no associations were detected between human milk nutritional contents and maternal dietary intake. Conclusion: In our study population, the composition of maternal diet and nutritional content of human milk differed between confinement and post-confinement periods. However, the association between maternal diet and human milk composition itself warrants further investigation.

Polyamine is a group of aliphatic amine that is necessary for cell growth and development. However, potential of developing cancer is enhanced with the increase of polyamine levels in the body. Since polyamines can be obtained through diet intake, it is essential for cancer patients to consume foods that have low level of polyamines. Therefore, this study aims to determine the polyamine level of selected plants; Sabah Snake Grass (Clinacanthus nutans), Daun Kadok (Piper sarmentosum) and Fig (Ficus auriculata). The antiproliferative effects of C. nutans, P. sarmentosum and F. auriculata were investigated using MTT assay and the polyamines content in these plants and intracellular content were quantified using High Performance Liquid Chromatography (HPLC). The results showed that polyamines content in C. nutans (41.49 nmol/g), P. sarmentosum (55.01 nmol/g) anf F. auriculata (39.28 nmol/g) were classified under low level. The IC50 values for these plants were in the range of 20-30 mg/ml. This study demonstrated that these plants inhibit the A549 cell’s growth after 24 hours to 96 hours of exposure. Depletion of intracellular polyamine after 48 hours to 96 hours of exposure was also identified. In conclusion, the study showed that C. nutans, P. sarmentosum and F.auriculata contain low level of polyamine and have anti-proliferative effect against A549 cells. Therefore these plants are recommended to reduce or delayed the occurrence of malignancy and prevention of cancer recurrence after successful treatment.