Displaying publications 21 - 40 of 45 in total

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  1. Inducing G2/M Cell Cycle Arrest and Apoptosis through Generation Reactive Oxygen Species (ROS)-Mediated Mitochondria Pathway in HT-29 Cells by Dentatin (DEN) and Dentatin Incorporated in Hydroxypropyl-β-Cyclodextrin (DEN-HPβCD)
    Ashwaq AS, Al-Qubaisi MS, Rasedee A, Abdul AB, Taufiq-Yap YH, Yeap SK
    Int J Mol Sci, 2016 Oct 18;17(10).
    PMID: 27763535
    Dentatin (DEN), purified from the roots of Clausena excavata Burm f., has poor aqueous solubility that reduces its therapeutic application. The aim of this study was to assess the effects of DEN-HPβCD (hydroxypropyl-β-cyclodextrin) complex as an anticancer agent in HT29 cancer cell line and compare with a crystal DEN in dimethyl sulfoxide (DMSO). The exposure of the cancer cells to DEN or DEN-HPβCD complex leads to cell growth inhibition as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To analyze the mechanism, in which DEN or DEN-HPβCD complex causes the death in human colon HT29 cancer cells, was evaluated by the enzyme-linked immunosorbent assay (ELIZA)-based assays for caspase-3, 8, 9, and reactive oxygen species (ROS). The findings showed that an anti-proliferative effect of DEN or DEN-HPβCD complex were via cell cycle arrest at the G2/M phase and eventually induced apoptosis through both mitochondrial and extrinsic pathways. The down-regulation of poly(ADP-ribose) polymerase (PARP) which leaded to apoptosis upon treatment, was investigated by Western-blotting. Hence, complexation between DEN and HPβCD did not diminish or eliminate the effective properties of DEN as anticancer agent. Therefore, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents in the future.
  2. Fulltext Mangifera indica L. kernel ethanol extract inhibits cell viability and proliferation with induction of cell cycle arrest and apoptosis in lung cancer cells
    Alshwyeh HA, Al-Sheikh WMS, Rasedee A, Alnasser SM, Al-Qubaisi MS, Ibrahim WN
    Mol Cell Oncol, 2024;11(1):2299046.
    PMID: 38196561 DOI: 10.1080/23723556.2023.2299046
    In this study, we investigated the effects of an ethanolic extract of Mangifera indica L. kernel on the viability and proliferation of human lung cancer cells. We utilized MTT and BrdU cell proliferation assays, morphological assessments, cell cycle analyses, and apoptosis assays to investigate the extract's effects on lung cancer (A549 and NCI-H292) and normal lung (MRC-5) cells. The extract demonstrated a toxicity toward cancer cells compared to normal cells with dose-dependent anti-proliferative effect on lung cancer cells. The extract also caused differential effects on the cell cycle, inducing G0/G1 arrest and increasing the Sub-G1 population in both lung cancer and normal lung cells. Notably, the extract induced loss of membrane integrity, shrinkage, membrane blebbing, and apoptosis in lung cancer cells, while normal cells exhibited only early apoptosis. Furthermore, the extract exhibited higher toxicity towards NCI-H292 cells, followed by A549 and normal MRC-5 cells in decreasing order of potency. Our results suggest that the ethanolic extract of M. indica L. kernel has significant potential as a novel therapeutic agent for treating lung cancer cells, given its ability to induce apoptosis in cancer cell lines while causing minimal harm to normal cells.
  3. Fulltext Green synthesis, characterization, and anticancer activity of hyaluronan/zinc oxide nanocomposite
    Namvar F, Azizi S, Rahman HS, Mohamad R, Rasedee A, Soltani M, et al.
    Onco Targets Ther, 2016;9:4549-59.
    PMID: 27555781 DOI: 10.2147/OTT.S95962
    The study describes an in situ green biosynthesis of zinc oxide nanocomposite using the seaweed Sargassum muticum water extract and hyaluronan biopolymer. The morphology and optical properties of the hyaluronan/zinc oxide (HA/ZnO) nanocomposite were determined by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, and ultraviolet-vis analysis. Electron microscopy and X-ray diffraction analysis showed that the zinc oxide nanoparticles were polydispersed with a mean size of 10.2±1.5 nm. The nanoparticles were mostly hexagonal in crystalline form. The HA/ZnO nanocomposite showed the absorption properties in the ultraviolet zone that is ascribed to the band gap of zinc oxide nanocomposite. In the cytotoxicity study, cancer cells, pancreatic adenocarcinoma (PANC-1), ovarian adenocarcinoma (CaOV-3), colonic adenocarcinoma (COLO205), and acute promyelocytic leukemia (HL-60) cells were treated with HA/ZnO nanocomposite. At 72 hours of treatment, the half maximal inhibitory concentration (IC50) value via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was 10.8±0.3 μg/mL, 15.4±1.2 μg/mL, 12.1±0.9 μg/mL, and 6.25±0.5 μg/mL for the PANC-1, CaOV-3, COLO-205, and HL-60 cells, respectively, showing that the composite is most toxic to the HL-60 cells. On the other hand, HA/ZnO nanocomposite treatment for 72 hours did not cause toxicity to the normal human lung fibroblast (MRC-5) cell line. Using fluorescent dyes and flow cytometry analysis, HA/ZnO nanocomposite caused G2/M cell cycle arrest and stimulated apoptosis-related increase in caspase-3 and -7 activities of the HL-60 cells. Thus, the study shows that the HA/ZnO nanocomposite produced through green synthesis has great potential to be developed into an efficacious therapeutic agent for cancers.
  4. Dietary protein influences on regulation of Haemonchus contortus populations in Dorsimal lambs
    Israf DA, Zainal MJ, Ben-Gheshir MA, Rasedee A, Sani RA, Noordin MM
    J Helminthol, 1998 Jun;72(2):143-6.
    PMID: 9687595
    The influence of dietary protein supplementation upon resistance to haemonchosis was examined in Dorsimal (Polled Dorset x Malin) lambs offered two levels of protein. Lambs were offered either a complete basal ruminant diet (15% crude protein (CP)) or the same diet supplemented with fish meal as a source of rumen bypass protein (19% CP). Lambs from each dietary treatment group were given either a 7-week trickle infection with Haemonchus contortus infective larvae (L3) or remained uninfected. All lambs were drenched with anthelmintic at week 8 post-infection (PI), challenged with a single dose of 5000 H. contortus L3 one week later, and killed 14 days post-challenge (PC). Lambs on the supplemented diet that were trickle infected showed a significant reduction in egg output. Supplementation and previous infection did not affect either growth rate, worm burden, worm development or haematological parameters. There was a trend for enhanced growth among supplemented non-infected lambs in comparison to lambs which received the basal ration.
  5. Fulltext Biomedical properties of a natural dietary plant metabolite, zerumbone, in cancer therapy and chemoprevention trials
    Rahman HS, Rasedee A, Yeap SK, Othman HH, Chartrand MS, Namvar F, et al.
    Biomed Res Int, 2014;2014:920742.
    PMID: 25025076 DOI: 10.1155/2014/920742
    Zerumbone (ZER) is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.
  6. Fulltext Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line
    Rahman HS, Rasedee A, Abdul AB, Zeenathul NA, Othman HH, Yeap SK, et al.
    Int J Nanomedicine, 2014;9:527-38.
    PMID: 24549090 DOI: 10.2147/IJN.S54346
    This investigation evaluated the antileukemia properties of a zerumbone (ZER)-loaded nanostructured lipid carrier (NLC) prepared by hot high-pressure homogenization techniques in an acute human lymphoblastic leukemia (Jurkat) cell line in vitro. The apoptogenic effect of the ZER-NLC on Jurkat cells was determined by fluorescent and electron microscopy, Annexin V-fluorescein isothiocyanate, Tdt-mediated dUTP nick-end labeling assay, cell cycle analysis, and caspase activity. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay showed that ZER-NLC did not have adverse effects on normal human peripheral blood mononuclear cells. ZER-NLC arrested the Jurkat cells at G2/M phase with inactivation of cyclin B1 protein. The study also showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, release of cytochrome c from the mitochondria into the cytosol, and subsequent cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP). These findings show that the ZER-NLC is a potentially useful treatment for acute lymphoblastic leukemia in humans.
  7. Fulltext Zerumbone-loaded nanostructured lipid carriers: preparation, characterization, and antileukemic effect
    Rahman HS, Rasedee A, How CW, Abdul AB, Zeenathul NA, Othman HH, et al.
    Int J Nanomedicine, 2013;8:2769-81.
    PMID: 23946649 DOI: 10.2147/IJN.S45313
    Zerumbone, a natural dietary lipophilic compound with low water solubility (1.296 mg/L at 25°C) was used in this investigation. The zerumbone was loaded into nanostructured lipid carriers using a hot, high-pressure homogenization technique. The physicochemical properties of the zerumbone-loaded nanostructured lipid carriers (ZER-NLC) were determined. The ZER-NLC particles had an average size of 52.68 ± 0.1 nm and a polydispersity index of 0.29 ± 0.004 μm. Transmission electron microscopy showed that the particles were spherical in shape. The zeta potential of the ZER-NLC was -25.03 ± 1.24 mV, entrapment efficiency was 99.03%, and drug loading was 7.92%. In vitro drug release of zerumbone from ZER-NLC was 46.7%, and for a pure zerumbone dispersion was 90.5% over 48 hours, following a zero equation. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human T-cell acute lymphoblastic leukemia (Jurkat) cells, the half maximal inhibitory concentration (IC50) of ZER-NLC was 5.64 ± 0.38 μg/mL, and for free zerumbone was 5.39 ± 0.43 μg/mL after 72 hours of treatment. This study strongly suggests that ZER-NLC have potential as a sustained-release drug carrier system for the treatment of leukemia.
  8. Fulltext Enhanced anti-mammary gland cancer activities of tamoxifen-loaded erythropoietin-coated drug delivery system
    Beh CY, Rasedee A, Selvarajah GT, Yazan LS, Omar AR, Foong JN, et al.
    PLoS One, 2019;14(7):e0219285.
    PMID: 31291309 DOI: 10.1371/journal.pone.0219285
    Nanomedicine is an emerging area in the medical field, particularly in the treatment of cancers. Nanostructured lipid carrier (NLC) was shown to be a good nanoparticulated carrier for the delivery of tamoxifen (TAM). In this study, the tamoxifen-loaded erythropoietin-coated nanostructured lipid carriers (EPO-TAMNLC) were developed to enhance the anti-cancer properties and targetability of TAM, using EPO as the homing ligand for EPO receptors (EpoRs) on breast cancer tissue cells. Tamoxifen-loaded NLC (TAMNLC) was used for comparison. The LA7 cells and LA7 cell-induced rat mammary gland tumor were used as models in the study. Immunocytochemistry staining showed that LA7 cells express estrogen receptors (ERs) and EpoRs. EPO-TAMNLC and TAMNLC significantly (p<0.05) inhibited proliferation of LA7 in dose- and time-dependent manner. EPO-TAMNLC induced apoptosis and G0/G1 cell cycle arrest of LA7 cells. Both drug delivery systems showed anti-mammary gland tumor properties. At an intravenous dose of 5 mg kg-1 body weight, EPO-TAMNLC and TAMNLC were not toxic to rats, suggesting that both are safe therapeutic compounds. In conclusion, EPO-TAMNLC is not only a unique drug delivery system because of the dual drug-loading feature, but also potentially highly specific in the targeting of breast cancer tissues positive for ERs and EpoRs. The incorporation of TAM into NLC with and without EPO coat had significantly (p<0.05) improved specificity and safety of the drug carriers in the treatment of mammary gland tumors.
  9. Fulltext Recombinant human Erythropoietin enhanced the cytotoxic effects of tamoxifen toward the spheroid MCF-7 breast cancer cells
    Shujaa Edin HY, Al-Haj NA, Rasedee A, Banu Alitheen N, Abdul Kadir A, Wun How C, et al.
    Saudi J Biol Sci, 2021 Sep;28(9):5214-5220.
    PMID: 34466099 DOI: 10.1016/j.sjbs.2021.05.043
    Erythropoietin (EPO) is widely used to treat anemia in patients undergoing chemotherapy for cancers. The main objective of this study was to investigate the effect of rHuEPO on the response of spheroid breast cancer, MCF-7, cells to tamoxifen treatment. The MCF-7 spheroids were treated with 10 mg/mL tamoxifen in combination with either 0, 10, 100 or 200 IU/mL rHuEPO for 24, 48 or 72 h. The viability of the MCF-7 cells was determined using the annexin-V, cell cycle, caspases activation and acridine orange/propidium iodide staining. rHuEPO-tamoxifen combination significantly (p greater than 0.05) increased the number of spheroid MCF-7 cells entering early apoptotic phase after 12 h and late apoptotic phase after 24 h of treatment; primarily the result of the antiproliferative effect tamoxifen. Tamoxifen alone significantly (p 
  10. Fulltext Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells
    Etti IC, Rasedee A, Hashim NM, Abdul AB, Kadir A, Yeap SK, et al.
    Drug Des Devel Ther, 2017;11:865-879.
    PMID: 28356713 DOI: 10.2147/DDDT.S124324
    Artonin E is a prenylated flavonoid compound isolated from the stem bark of Artocarpus elasticus. This phytochemical has been previously reported to be drug-like with full compliance to Lipinski's rule of five and good physicochemical properties when compared with 95% of orally available drugs. It has also been shown to possess unique medicinal properties that can be utilized in view of alleviating most human disease conditions. In this study, we investigated the cytotoxic mechanism of Artonin E in MCF-7 breast cancer cells, which has so far not been reported. In this context, Artonin E significantly suppressed the breast cancer cell's viability while inducing apoptosis in a dose-dependent manner. This apoptosis induction was caspase dependent, and it is mediated mainly through the intrinsic pathway with the elevation of total reactive oxygen species. Gene and protein expression studies revealed significant upregulation of cytochrome c, Bax, caspases 7 and 9, and p21 in Artonin E-treated MCF-7 cells, while MAPK and cyclin D were downregulated. Livin, a member of the inhibitors of apoptosis, whose upregulation has been noted to precede chemotherapeutic resistance and apoptosis evasion was remarkably repressed. In all, Artonin E stood high as a potential agent in the treatment of breast cancer.
  11. Fulltext Zerumbone-Loaded Nanostructured Lipid Carrier Induces Apoptosis of Canine Mammary Adenocarcinoma Cells
    Foong JN, Selvarajah GT, Rasedee A, Rahman HS, How CW, Beh CY, et al.
    Biomed Res Int, 2018;2018:8691569.
    PMID: 30410940 DOI: 10.1155/2018/8691569
    Canine mammary gland tumor (CMT) is the most common tumor in intact female dog. Zerumbone (ZER) has promising anticancer properties, but plagued with poor water solubility, poor absorption, bioavailability, and delivery to target tissues. To solubilize, ZER was loaded into nanostructured lipid carrier (NLC) to produce ZER-loaded NLC (ZER-NLC). The objectives of this study were to determine the antiproliferative effect and the mode of cell death induced by ZER-NLC and ZER on a canine mammary gland tumor (CMT) adenocarcinoma primary cell line. There was no significant difference (p>0.05) between ZER-NLC and ZER treatments in the inhibition of CMT cell proliferation; thus, the loading of ZER into NLC did not compromise the cytotoxic effect of ZER. Microscopically, ZER-NLC- and ZER-treated CMT cells showed apoptotic cell morphology. ZER-NLC and ZER treatments significantly downregulated the antiapoptotic Bcl-2 and upregulated the proapoptotic Bax gene expressions in CMT cells. Both ZER-NLC and ZER-treated CMT cells showed significant (p<0.0001) increases in caspase-8, -9, and -3/7 protein activities. In conclusion, ZER-NLC induced CMT cell death via regulation of Bcl-2 and Bax gene expressions and caspase activations, indicating the involvement of both the intrinsic and extrinsic pathways of apoptosis. This study provided evidences for the potential of ZER-NLC as an anticanine mammary gland adenocarcinoma chemotherapy.
  12. In vivo antitrypanosomal activity of Garcinia hombroniana aqueous extract
    Dyary HO, Arifah AK, Sharma RS, Rasedee A, Mohd Aspollah MS, Zakaria ZA, et al.
    Res Vet Sci, 2015 Jun;100:226-31.
    PMID: 25818171 DOI: 10.1016/j.rvsc.2015.03.007
    The anti-Trypanosoma evansi activity of Garcinia hombroniana (seashore mangosteen) leaves aqueous extract was tested on experimentally infected Sprague-Dawley rats. Treatment of infected rats with G. hombroniana extract resulted in a significantly extended post-infection longevity (p 
  13. Fulltext Anticancer effect of dentatin and dentatin-hydroxypropyl-β-cyclodextrin complex on human colon cancer (HT-29) cell line
    Al-Abboodi AS, Rasedee A, Abdul AB, Taufiq-Yap YH, Alkaby WAA, Ghaji MS, et al.
    Drug Des Devel Ther, 2017;11:3309-3319.
    PMID: 29200826 DOI: 10.2147/DDDT.S147626
    Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-β-cyclodextrin (HPβCD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HPβCD complex were demonstrated in human colon HT-29 cancer cells.

    Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HPβCD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins.

    Results: At 3, 6, 12, and 24 µg/mL exposure, DEN and DEN-HPβCD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HPβCD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9.

    Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HPβCD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HPβCD complex may have chemotherapeutic benefits for colon cancer patients.

  14. Fulltext Recombinant Human erythropoietin reduces viability of MCF-7 breast cancer cells from 3D culture without caspase activation
    ShujaaEdin HY, Al-Haj NA, Rasedee A, Alitheen NB, Kadir AA, How CW, et al.
    Saudi J Biol Sci, 2021 Apr;28(4):2549-2557.
    PMID: 33935571 DOI: 10.1016/j.sjbs.2021.01.059
    Recombinant human erythropoietin (rHuEPO) is the erythropoiesis-stimulating hormone that is being used concurrently with chemotherapeutic drugs in the treatment of anemia of cancer. The effect of rHuEPO on cancer cells in 3-dimensional (3D) cultures is not known. The objective of the study was to determine the effect of rHuEPO on the viability of MCF-7 breast cancer cells from 2-dimensional (2D) and 3D cell cultures. The monolayer MCF-7 cells from 2D culture and MCF-7 cell from 3D culture generated by ultra-low adhesive microplate technique, were treated with 0, 0.1, 10, 100 or 200 IU/mL rHuEPO for 24, 48 or 72 h. The effects of rHuEPO on MCF-7 cell viability and proliferation were determined using the (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT), neutral red retention time (NRRT), trypan blue exclusion assay (TBE), DNA fragmentation, acridine orange/propidium iodide staining (AO/PI) assays. The MCF-7 cells for 3D culture were also subjected to caspase assays and cell cycle analysis using flow cytometry. rHuEPO appeared to have greater effect at lowering the viability of MCF-7 cells from 3D than 2D cultures. rHuEPO significantly (p 
  15. Fulltext Physicochemical properties, cytotoxicity, and antimicrobial activity of sulphated zirconia nanoparticles
    Mftah A, Alhassan FH, Al-Qubaisi MS, El Zowalaty ME, Webster TJ, Sh-Eldin M, et al.
    Int J Nanomedicine, 2015;10:765-74.
    PMID: 25632233 DOI: 10.2147/IJN.S66058
    Nanoparticle sulphated zirconia with Brønsted acidic sites were prepared here by an impregnation reaction followed by calcination at 600°C for 3 hours. The characterization was completed using X-ray diffraction, thermal gravimetric analysis, Fourier transform infrared spectroscopy, Brunner-Emmett-Teller surface area measurements, scanning electron microscopy with energy dispersive X-ray spectroscopy, and transmission electron microscopy. Moreover, the anticancer and antimicrobial effects were investigated for the first time. This study showed for the first time that the exposure of cancer cells to sulphated zirconia nanoparticles (3.9-1,000 μg/mL for 24 hours) resulted in a dose-dependent inhibition of cell growth, as determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Similar promising results were observed for reducing bacteria functions. In this manner, this study demonstrated that sulphated zirconia nanoparticles with Brønsted acidic sites should be further studied for a wide range of anticancer and antibacterial applications.
  16. Fulltext Acute toxicity study of zerumbone-loaded nanostructured lipid carrier on BALB/c mice model
    Rahman HS, Rasedee A, Othman HH, Chartrand MS, Namvar F, Yeap SK, et al.
    Biomed Res Int, 2014;2014:563930.
    PMID: 25276798 DOI: 10.1155/2014/563930
    Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.
  17. Wide dynamic range of surface-plasmon-resonance-based assay for hepatitis B surface antigen antibody optimal detection in comparison with ELISA
    Tam YJ, Zeenathul NA, Rezaei MA, Mustafa NH, Azmi MLM, Bahaman AR, et al.
    Biotechnol Appl Biochem, 2017 Sep;64(5):735-744.
    PMID: 27506960 DOI: 10.1002/bab.1528
    Limit of detection (LOD), limit of quantification, and the dynamic range of detection of hepatitis B surface antigen antibody (anti-HBs) using a surface plasmon resonance (SPR) chip-based approach with Pichia pastoris-derived recombinant hepatitis B surface antigen (HBsAg) as recognition element were established through the scouting for optimal conditions for the improvement of immobilization efficiency and in the use of optimal regeneration buffer. Recombinant HBsAg was immobilized onto the sensor surface of a CM5 chip at a concentration of 150 mg/L in sodium acetate buffer at pH 4 with added 0.6% Triton X-100. A regeneration solution of 20 mM HCl was optimally found to effectively unbind analytes from the ligand, thus allowing for multiple screening cycles. A dynamic range of detection of ∼0.00098-0.25 mg/L was obtained, and a sevenfold higher LOD, as well as a twofold increase in coefficient of variance of the replicated results, was shown as compared with enzyme-linked immunosorbent assay (ELISA). Evaluation of the assay for specificity showed no cross-reactivity with other antibodies tested. The ability of SPR chip-based assay and ELISA to detect anti-HBs in human serum was comparable, indicating that the SPR chip-based assay with its multiple screening capacity has greater advantage over ELISA.
  18. Characterization of thymoquinone/hydroxypropyl-β-cyclodextrin inclusion complex: Application to anti-allergy properties
    Al-Qubaisi MS, Rasedee A, Flaifel MH, Eid EEM, Hussein-Al-Ali S, Alhassan FH, et al.
    Eur J Pharm Sci, 2019 May 15;133:167-182.
    PMID: 30902654 DOI: 10.1016/j.ejps.2019.03.015
    Thymoquinone is an effective phytochemical compound in the treatment of various diseases. However, its practical administration has been limited due to poor aqueous solubility and bioavailability. In this work, we developed a novel inclusion complex of thymoquinone and hydroxypropyl-β-cyclodextrin that features improved solubility and bioactivity. The drug solubility was markedly accelerated in the increasing ratio of hydroxypropyl-β-cyclodextrin to thymoquinone amount. The formation of the thymoquinone/hydroxypropyl-β-cyclodextrin inclusion complex was evidenced using X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, Fourier transform infrared, scanning electron microscopy and nuclear magnetic resonance. The release behavior of the complex, as well as of their mixtures, was examined in artificial gastric (pH 1.2) and intestinal (pH 6.8) dissolution media. The formulated complex released the drug rapidly at the initial stage, followed by a slow release. Thermodynamic parameters ΔH, ΔS and ΔG were calculated with temperatures ranging from 20 to 45 °C to evaluate the complexation process. The activity of the inclusion complex was evaluated on IgE-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells by monitoring key allergic mediators. The results revealed that compared with free thymoquinone, the inclusion complex more strongly inhibited the release of histamine, tumor necrosis factor-α, and interleukin-4, and was not cytotoxic at the tested thymoquinone concentrations (0.125-4 μg/mL) indicating the inclusion complex possibly had better antiallergic effects. Our finding suggested that the inclusion complex achieved prolonged action and reduced side-effect of thymoquinone.
  19. Fulltext Effect of fetal bovine serum on erythropoietin receptor expression and viability of breast cancer cells
    Teo GY, Rasedee A, Al-Haj NA, Beh CY, How CW, Rahman HS, et al.
    Saudi J Biol Sci, 2020 Feb;27(2):653-658.
    PMID: 32210684 DOI: 10.1016/j.sjbs.2019.11.032
    Erythropoietin receptors (EPORs) are present not only in erythrocyte precursors but also in non-hematopoietic cells including cancer cells. In this study, we determined the effect of fetal bovine serum (FBS) in culture medium on the EPOR expression and viability of the estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Using flow cytometry, we showed that the inclusion of 10% FBS in the medium increased the EPOR expressions and viabilities of MDA-MB-231 and MCF-7 cells. The MDA-MB-231 showed greater EPOR expression than MCF-7 cells, suggesting that the presence of ERs on cells is associated with poor expression of EPOR. Culture medium containing 10% FBS also caused increased number of breast cancer cells entering the synthesis phase of the cell cycle. The study also showed that rHuEPO treatment did not affect viability of breast cancer cells. In conclusion, it was shown that the inclusion of FBS in culture medium increased expression of EPOR in breast cancer cells and rHuEPO treatment had no effect on the proliferation of these cancer cells.
  20. Fulltext Cytotoxicity and physicochemical characterization of iron-manganese-doped sulfated zirconia nanoparticles
    Al-Fahdawi MQ, Rasedee A, Al-Qubaisi MS, Alhassan FH, Rosli R, El Zowalaty ME, et al.
    Int J Nanomedicine, 2015;10:5739-50.
    PMID: 26425082 DOI: 10.2147/IJN.S82586
    Iron-manganese-doped sulfated zirconia nanoparticles with both Lewis and Brønsted acidic sites were prepared by a hydrothermal impregnation method followed by calcination at 650°C for 5 hours, and their cytotoxicity properties against cancer cell lines were determined. The characterization was carried out using X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, Brauner-Emmett-Teller (BET) surface area measurements, X-ray fluorescence, X-ray photoelectron spectroscopy, zeta size potential, and transmission electron microscopy (TEM). The cytotoxicity of iron-manganese-doped sulfated zirconia nanoparticles was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays against three human cancer cell lines (breast cancer MDA-MB231 cells, colon carcinoma HT29 cells, and hepatocellular carcinoma HepG2 cells) and two normal human cell lines (normal hepatocyte Chang cells and normal human umbilical vein endothelial cells [HUVECs]). The results suggest for the first time that iron-manganese-doped sulfated zirconia nanoparticles are cytotoxic to MDA-MB231 and HepG2 cancer cells but have less toxicity to HT29 and normal cells at concentrations from 7.8 μg/mL to 500 μg/mL. The morphology of the treated cells was also studied, and the results supported those from the cytotoxicity study in that the nanoparticle-treated HepG2 and MDA-MB231 cells had more dramatic changes in cell morphology than the HT29 cells. In this manner, this study provides the first evidence that iron-manganese-doped sulfated zirconia nanoparticles should be further studied for a wide range of cancer applications without detrimental effects on healthy cell functions.
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