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@#Introduction: Nanoparticles exhibit unique features and currently at the forefront of cutting-edge research. Silver nanoparticles (AgNPs) are among the most promising and widely commercialised nanoproducts in various fields. The interaction of these AgNPs with cells remain unclear to connect with its toxicological endpoints. The aim of this study was to investigate the cellular uptake of C. roseus-AgNPs in hepatocellular carcinoma cells HepG2. Methods: The HepG2 cells were treated with the mean IC50 value of C. roseus-AgNPs which was 4.95±0.26 µg/mL for 24, 48 and 72 hours. The effects were compared with the untreated cells and other treatments which include camptothecin, C. roseus-aqueous extract, and AgNO3 . Inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to quantify the intracellular Ag+ and Ca2+, while transmission electron microscopy (TEM) imaging was used to visualise the nanoparticle distribution. Results: The HepG2 cells have significantly taken up Ag+ from C. roseus-AgNPs with at least six times higher compared to Ag+ from AgNO3 . The intracellular Ca2+ detected in HepG2 cells for all treatments were significantly higher than the untreated cells, in time-dependent manner. TEM images indicated the endocytosis of C. roseus-AgNPs with the presence of endosomes and exocytic vesicles. Conclusion: The significant accumulation of intracellular Ag+ demonstrated the efficiency of the C. roseus-AgNPs uptake while the increased Ca2+ indicated the early sign of cell injury. The cellular uptake was mainly through endocytosis. These findings are crucial to correlate the physicochemical properties of C. roseus-AgNPs with the anticancer mechanisms towards the development of liver cancer therapy.
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Abstract@#Introduction: Goniothalamin (GTN) is a plant styryl-lactone that has been reported to possess anticancer properties. However, limited studies were conducted to explore the selectivity of GTN to human cancer cells in comparison with normal human cells counterpart. The aim of this study was to evaluate the cytotoxicity and selectivity of GTN in human cancer cells lines of osteosarcoma cells (Saos-2), adenocarcinoma alveolar basal epithelial cells (A549), breast carcinoma cells (UACC-732), breast adenocarcinoma cells (MCF-7), colorectal adenocarcinoma cells (HT29). Human bone marrow-derived mesenchymal stem cells (HMSC) served as a control normal cell. Methods: The antiproliferative activity of GTN was assessed by MTT assay for 24, 48 and 72 h of incubation time. Then, the half maximal inhibitory concentration (IC50) and the selectivity index (S.I) were calculated to examine the potency and selectivity of GTN. Results: GTN has significantly exhibited concentration and time-dependent inhibitory effect to all tested cancer cells with the lowest IC50 values ranging from 0.62±0.06 to 2.01±0.28 µg/ml after 72 h. Besides, GTN was found to be better than doxorubicin, DOX (positive control) in term of its selectivity towards cancer cells as higher S.I values between 2.86±0.31 to 10.02±1.49 were determined for all the cancer cells. Conclusion: This study concludes that GTN fulfills the basic criteria as an effective therapeutic agent by possessing a very strong range of anticancer activity with less toxicity towards the normal cells. Thus, GTN could be considered as a promising alternative to present chemotherapeutic drug in cancer treatment.
ABSTRACT
Abstract@#Introduction: The alkaloids present in Catharanthus roseus (C. roseus), vinblastine and vincristine are important anticancer agents that cause cell cycle arrest and apoptosis in various types of cell lines. However, there is no previous reports that emphasized the clear mechanisms of anticancer exerted by a crude aquoeus extract of C. roseus although it has been historically used to treat various diseases. Methods: The cytotoxicity effects of C. roseus aqueous extract on Jurkat cells were evaluated by annexin/PI staining, caspase 3/7 assay, JC-1 assay and cell cycle assay. Gene expression profiling was performed by using SmartChip Real-Time PCR system to evaluate the expression profiles of oncology-related genes of Jurkat cells treated with C. roseus aqueous extract. Results: Flow cytometry analysis revealed that the extract has caused S-phase arrest and associated with apoptosis through the externalization of phosphatidylserine and depletion of mitochondrial membrane potential in time-dependent manner. The apoptosis mechanism was mediated through the activation of caspase 3/7. From the gene expression analysis, 8 differentially regulated genes were associated with apoptosis which were CDKN1C, CHI3L2, BIRC8, GFER, ID3-1, BBC3-2, TRAF4 and VCAN. Meanwhile, 7 differentially regulated genes were associated with cell cycle progression which were PIMI-1, CDKN1C, SKP1A, CDC25C, LTBP1, CCNG2 and RBL1. Conclusion: The recent data may facilitate the identification of specific targeting pathways induced by the extract. The information obtained may be used as diagnostic tools, prognostic markers, and predictors of response to C. roseus treatment especially for this particular type of cancer.