[Show abstract][Hide abstract] ABSTRACT: Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, the lymphatic system, or by direct extension. In case of hepatocellularcarcinoma, cancer cells acquire the ability to penetrate the walls of lymphatic and/or blood vessels, after which they are able to circulate through the bloodstream (circulating tumor cells) to other sites and tissues in the body and come to rest at another site, they re-penetrate the vessel or walls and continue to multiply, eventually forming another clinically detectable tumor known as a metastatic or secondary tumor implant. Recently, antileukemia properties of Zerumbone (ZER)-loaded nanostructured lipid carrier (NLC) prepared by hot high-pressure homogenization (HPH) techniques on acute human lymphoblastic leukemia (Jurkat) cell line in vitro were investigated by fluorescent and electron microscopy, annexinV-FITC, TUNEL assay, cell cycle analysis and caspase activities. However, the aim of this investigation is to determine the anti-metastatic activity of ZER-NLC in experimentally induced hepatocarcinoma in BALB/c mice model using immunohistochemistry to detect special biomarkers such as CD31, VEGF, MMP9 and KI167.
26th Veterinary Association Malaysia-2014, Palm Garden Hotel IOI Resort, 62502 Putrajaya Malaysia; 06/2014
[Show abstract][Hide abstract] ABSTRACT: 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 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 of 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. Therapeutica 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 treatment of malignancies using ZER.
BioMed Research International 06/2014; 2014(920742):20 pages. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immunomodulators are agents that are able to stimulate or inhibit the immune response. The leaf extracts from Potentilla indica and Dendrophthoe pentandra were analyzed in vitro for immunomodulatory activity and an MTT colorimetric assay was conducted to determine the proliferation of mice splenocytes and thymocytes. A bromodeoxyuridine assay was performed to analyze DNA synthesis and the Trypan blue exclusion method was conducted to evaluate the changes in total cell population. The results indicated that treatment with P. indica and D. pentandra produced a time- and dose-dependent increase in cell viability and proliferation. Following 72 h of treatment with P. indica and D. pentandra, thymocyte proliferation was augmented by 18 and 41%, respectively and splenocyte proliferation increased by 35 and 42%, respectively, when compared with untreated cells. The present study demonstrated that these extracts may act as potential immunostimulants and, thus, represent an alternative source of immunomodulatory compounds for the treatment of human immune-mediated diseases.
Experimental and therapeutic medicine 06/2014; 7(6):1733-1737. · 0.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases, including cancer. Although noni has long been consumed in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In the present study, the effect of damnacanthal on MCF-7 cell growth regulation was investigated. Treatment of MCF-7 cells with damnacanthal for 72 h indicated an antiproliferative activity. The MTT method confirmed that damnacanthal inhibited the growth of MCF-7 cells at the concentration of 8.2 μg/ml for 72 h. In addition, the drug was found to induce cell cycle arrest at the G1 checkpoint in MCF-7 cells by cell cycle analysis. Damnacanthal induced apoptosis, determined by Annexin V-fluorescein isothiocyanate/propidium iodide (PI) dual-labeling, acridine-orange/PI dyeing and caspase-7 expression. Furthermore, damnacanthal-mediated apoptosis involves the sustained activation of p21, leading to the transcription of p53 and the Bax gene. Overall, the present study provided significant evidence demonstrating that p53-mediated damnacanthal induced apoptosis through the activation of p21 and caspase-7.
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Nanomedicine 01/2014; 9:527-38. · 3.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA) is an immunodetection method that can quantify PCR product directly after immobilization of biotinylated DNA on a microplate. This method, which detects nucleic acid instead of protein, is a much more sensitive method compared to conventional PCR method, with shorter analytical time and lower detection limit. Its high specificity and sensitivity, together with its semiquantitative ability, give it a huge potential to serve as a powerful detection tool in various industries such as medical, veterinary, and agricultural industries. With the recent advances in PCR-ELISA, it is envisaged that the assay is more widely recognized for its fast and sensitive detection limit which could improve overall diagnostic time and quality.
BioMed Research International 01/2014; 2014:653014. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mung bean has been traditionally used to alleviate heat stress. This effect may be contributed by the presence of flavonoids and γ -aminobutyric acid (GABA). On the other hand, fermentation and germination have been practised to enhance the nutritional and antioxidant properties of certain food products. The main focus of current study was to compare the antistress effect of none-process, fermented and germinated mung bean extracts. Acute and chronic restraint stresses were observed to promote the elevation of serum biochemical markers including cholesterol, triglyceride, total protein, liver enzymes, and glucose. Chronic cold restraint stress was observed to increase theadrenal gland weight, brain 5-hydroxytryptamine (5-HT), and malondialdehyde (MDA) level while reducing brain antioxidant enzyme level. However, these parameters were found reverted in mice treated with diazepam, high concentration of fermented mung bean and high concentration of germinated mung bean. Moreover, enhanced level of antioxidant on the chronic stress mice was observed in fermented and germinated mung bean treated groups. In comparison between germinated and fermented mung bean, fermented mung bean always showed better antistress and antioxidant effects throughout this study.
BioMed Research International 01/2014; 2014:694842. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fermented red yeast rice has been traditionally consumed as medication in Asian cuisine. This study aimed to determine the in vivo hypocholesterolemic and antioxidant effects of fermented red yeast rice water extract produced using Malaysian Agricultural Research and Development Institute (MARDI) Monascus purpureus strains in mice fed with high cholesterol diet. Absence of monacolin-k, lower level of γ-aminobutyric acid (GABA), higher content of total amino acids, and antioxidant activities were detected in MARDI fermented red yeast rice water extract (MFRYR). In vivo MFRYR treatment on hypercholesterolemic mice recorded similar lipid lowering effect as commercial red yeast rice extract (CRYR) as it helps to reduce the elevated serum liver enzyme and increased the antioxidant levels in liver. This effect was also associated with the upregulation of apolipoproteins-E and inhibition of Von Willebrand factor expression. In summary, MFRYR enriched in antioxidant and amino acid without monacolin-k showed similar hypocholesterolemic effect as CRYR that was rich in monacolin-k and GABA.
Evidence-based complementary and alternative medicine : eCAM. 01/2014; 2014:707829.
[Show abstract][Hide abstract] ABSTRACT: Vitamin C is generally thought to enhance immunity and is widely taken as a supplement especially during cancer treatment. Tamoxifen (TAM) has both cytostatic and cytotoxic properties for breast cancer. TAM engaged mitochondrial oestrogen receptor beta in MCF-7 cells and induces apoptosis by activation of pro-caspase-8 followed by downstream events, including an increase in reactive oxygen species and the release of pro-apoptotic factors from the mitochondria. In addition to that, TAM binds with high affinity to the microsomal anti-oestrogen-binding site and inhibits cholesterol esterification at therapeutic doses. This study aimed to investigate the role of vitamin C in TAM-mediated apoptosis. Cells were loaded with vitamin C by exposure to dehydroascorbic acid, thereby circumventing in vitro artefacts associated with the poor transport and pro-oxidant effects of ascorbic acid. Pre-treatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by acridine-orange/propidium iodide (AO/PI) and Annexin V assay after treatment with TAM. Vitamin C dose-dependently protected cancer cells against lipid peroxidation caused by TAM treatment. By real-time PCR analysis, an impressive increase in FasL and tumour necrosis factor-α (TNF-α) mRNA was detected after TAM treatment. In addition, a decrease in mitochondrial transmembrane potential was observed. These results support the hypothesis that vitamin C supplementation during cancer treatment may detrimentally affect therapeutic response.
Journal of Cellular and Molecular Medicine 11/2013; · 4.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Plant-based compounds have been in the spotlight in search of new and promising drugs. Flavokawain A, B and C are naturally occurring chalcones that have been isolated from several medicinal plants; namely the piper methysticum or commercially known as the kava-kava. Multiple researches have been done to evaluate the bioactivities of these compounds. It has been shown that all three flavokawains may hold promising anti-cancer effects. It has also been revealed that both flavokawain A and B are involved in the induction of cell cycle arrest in several cancer cell lines. Nevertheless, flavokawain B was shown to be more effective in treating in vitro cancer cell lines as compared to flavokawain A and C. Flavokawain B also exerts antinociceptive effects as well as anti-inflammation properties. This mini-review attempts to discuss the biological properties of all the flavokawains that have been reported.
Cancer Cell International 10/2013; 13(1):102. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Noni fruit, or scientifically known as Morinda Citrifolia can be found in various parts of the world, especially in the pacific region. It is a small evergreen bushy-like tree originated from the Rubiaceae family. The plant has been used by polynesians as a medicinal herb for more than 2000 years. A substantial amount of phytochemicals can be found in the roots of this plant. Among all, damnacanthal has been found to be the most interesting, versatile and potent compound. Damnacanthal or chemically known as, 3 - hydroxy-1-methoxyanthraquinone -2-caboxaldehyde (C16H10O5), appears as pale yellow crystals with a melting point of 210-211°C. This compound is of particular interest due to its striking pharmacological properties. Damnacanthal was shown to inhibit the oncogene Ras, p56lck tyrosine kinase, NF-KB pathway and induce apoptosis in vitro. This review aims to discuss the biological properties of damnacanthal, specifically on its anti-cancer activity that has been reported.
Anti-cancer agents in medicinal chemistry 10/2013;
[Show abstract][Hide abstract] ABSTRACT: Newcastle disease (ND) is a highly contagious avian disease and one of the major causes of economic losses in the poultry industry. The emergence of virulent NDV genotypes and repeated outbreaks of NDV in vaccinated chickens have raised the need for fundamental studies on the virus-host interactions. In this study, the profiles of B and T lymphocytes and macrophages and differential expression of 26 immune-related genes in the spleen of specific-pathogen-free (SPF) chickens, infected with either the velogenic genotype VII NDV strain IBS002 or the genotype VIII NDV strain AF2240, were evaluated. A significant reduction in T lymphocyte population and an increase in the infiltration of IgM(+) B cells and KUL01(+) macrophages were detected in the infected spleens at 1, 3 and 4 days post-infection (dpi) (P<0.05). The gene expression profiles showed an up-regulation of CCLi3, CXCLi1, CXCLi2 (IL-8), IFN-γ, IL-12α, IL-18, IL-1β, IL-6, iNOS, TLR7, MHCI, IL-17F and TNFSF13B (P<0.05). However, these two genotypes showed different cytokine expression patterns and viral load. IBS002 showed higher viral load than AF2240 in spleen at 3 and 4dpi and caused a more rapid up-regulation of CXCLi2, IFN-γ, IL-12α, IL-18, IL-1β, iNOS and IL-10 at 3dpi. Meanwhile, the expression levels of CCLI3, CXCLi1, IFN-γ, IL-12α, IL-1β and iNOS genes were significantly higher in AF2240 at 4dpi. In addition, the expression levels of IL-10 were significantly higher in the IBS002-infected chickens at 3 and 4dpi. Hence, infection with velogenic genotype VII and VIII NDV induced different viral load and production of cytokines and chemokines associated with inflammatory reactions.
[Show abstract][Hide abstract] ABSTRACT: The aim of this investigation is to evaluate the anticancer properties of Zerumbone nanostructured lipid carrier (ZER-NLC) prepared by hot high pressure homogenization (HPH) techniques on cancer cells of T-acute lymphoblastic leukemia, Jurkat cells using MTT assay together with microscopy investigations (fluorescent microscope and electron microscope) and flow cytometric analysis (annexinV-FITC, cell cycle and TUNEL assay). We demonstrated here for the first time that ZER-NLC significantly (P < 0.05) suppressed the proliferation of Jurkat cells in time dependent manner at 24, 48 and 72 h, while not affecting normal blood mononuclear cells. The current finding concluded that ZER-NLC might be useful as an anticancer agent for acute lymphocytic leukemia (ALL).
International Congress on Natural Products, Mashhad-Iran; 09/2013
[Show abstract][Hide abstract] ABSTRACT: We had examined the immunogenicity of a series of plasmid DNAs which include neuraminidase (NA) and nucleoprotein (NP) genes from avian influenza virus (AIV). The interleukin-15 (IL-15) and interleukin-18 (IL-18) as genetic adjuvants were used for immunization in combination with the N1 and NP AIV genes. In the first trial, 8 groups of chickens were established with 10 specific-pathogen-free (SPF) chickens per group while, in the second trial 7 SPF chickens per group were used. The overall N1 enzyme-linked immunosorbent assay (ELISA) titer in chickens immunized with the pDis/N1+pDis/IL-15 was higher compared to the chickens immunized with the pDis/N1 and this suggesting that chicken IL-15 could play a role in enhancing the humoral immune response. Besides that, the chickens that were immunized at 14-day-old (Trial 2) showed a higher N1 antibody titer compared to the chickens that were immunized at 1-day-old (Trial 1). Despite the delayed in NP antibody responses, the chickens co-administrated with IL-15 were able to induce earlier and higher antibody response compared to the pDis/NP and pDis/NP+pDis/IL-18 inoculated groups. The pDis/N1+pDis/IL-15 inoculated chickens also induced higher CD8+ T cells increase than the pDis/N1 group in both trials (P<0.05). The flow cytometry results from both trials demonstrated that the pDis/N1+pDis/IL-18 groups were able to induce CD4+ T cells higher than the pDis/N1 group (P<0.05). Meanwhile, pDis/N1+pDis/IL-18 group was able to induce CD8+ T cells higher than the pDis/N1 group (P<0.05) in Trial 2 only. In the present study, pDis/NP was not significant (P>0.05) in inducing CD4+ and CD8+ T cells when co-administered with the pDis/IL-18 in both trials in comparison to the pDis/NP. Our data suggest that the pDis/N1+pDis/IL-15 combination has the potential to be used as a DNA vaccine against AIV in chickens.
Research in Veterinary Science 08/2013; · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rhaphidophora korthalsii (Araceae) is a root-climber plant which has been widely used in Chinese traditional medicine for cancer and skin disease treatment. Previous reports have recorded its immunomodulatory effects on mice splenocyte and human peripheral blood. This study investigated the potential immunostimulatory effect of Rhaphidophora korthalsii on human PBMC enriched NK cell.
PBMC was exposed to various concentrations of R. korthalsii extract and the T and NK cell population in the control and extract treated PBMC were identified by immunophenotyping. Intracellular perforin and granzyme B expressions were detected by flow cytometry and extra-cellular Granzyme B, IFN-gamma and TNF-alpha production in the isolated NK cells were determined by ELISA. The cytotoxicity of effector NK cell towards target K562 cell was assessed by CytoTox 96 assay.
Rhaphidophora korthalsii methanol extract significantly increased PBMC NK cell population and intracellular perforin and granzyme B expressions. Moreover, the extract also enhanced the secretion of IFN-gamma and TNF-alpha which subsequently enhanced the cytotoxicity of NK cell against the NK sensitive target K562 cell line. NK cell enriched with extract treated PBMC showed better activation than NK cell directly treated with the extract.
Our findings indicated a potential IL-2 free immunotherapy through direct and indirect R. korthalsii stimulation on NK cell activation.
BMC Complementary and Alternative Medicine 06/2013; 13(1):145. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Goniothalamin is a biologically active styrylpyrone derivative isolated from various Goniothalamus species. The ability of goniothalamin to induce apoptosis via caspase-3 activation against hepatoblastoma (HepG2) and normal liver cells (Chang cells) was studied using morphological and biochemical evaluations. HepG2 and Chang cells were treated with goniothalamin for 72 h and analysed by TUNEL and Annexin-V/PI staining. Furthermore, the post-mitochondrial caspase-3 was quantified using ELISA. In view of our results, goniothalamin induced apoptosis on treated cells via alteration of cellular membrane integrity and cleavage of DNA. On the other hand, post-mitochondrial caspase-3 activity was significantly elevated in HepG2 cells treated with goniothalamin after 72 h. These findings suggest that goniothalamin induced apoptosis on HepG2 liver cancer cells via induction of caspase-3 with less sensitivity on the cell line of Chang cells.
Natural product research 06/2013; · 1.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Goniothalamin is a biologically active styrylpyrone derivative isolated from various Goniothalamus species. The ability of goniothalamin to induce apoptosis via caspase-3 activation against hepatoblastoma (HepG2) and normal liver cells (Chang cells) was studied using morphological and biochemical evaluation. HepG2 and Chang cells were treated with goniothalamin for 72 h and analyzed by TUNEL and Annexin-V/PI staining. Furthermore the post-mitochondrial caspase-3 was quantified using ELISA. In view of our results, goniothalamin induced apoptosis on treated cells via alteration of cellular membrane integrity and cleavage of DNA. On the other hand, post-mitochondrial caspase-3 activity was significantly elevated in HepG2 cells treated with goniothalamin after 72 h. These findings suggest that goniothalamin induced apoptosis on HepG2 liver cancer cells via induction of caspase-3 with less sensitivity on normal liver Chang cell line.
Natural Product Research 04/2013; · 1.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A phage display library of single chain variable fragment (scFv) against MCF-7 breast cancer cells was constructed from C3A8 hybridoma cells. RNA from the C3A8 was isolated, cDNA was constructed, and variable heavy and variable light immunoglobulin chain gene region were amplified using PCR. The variable heavy and light chain gene regions were combined with flexible linker, linked to a pCANTAB 5E phagemid vector and electrophoresed into supE strain of E. coli TG1 cells. Forty-eight clones demonstrated positive binding activity to MCF-7 breast cancer cell membrane fragments and the strongest of 48 clones was selected for analysis. The anti-MCF-7 library evaluated by SfiI and NotI digests demonstrated that anti-MCF-7 scFv antibodies possess individual patterns that should be able to recognize distinct human breast cancer cells. The C3A8 scFv, with an apparent molecular weight of 32kDa, showed high homology (99%) with single chain antibody against rice stripe virus protein P20. In summary, the anti MCF-7 scFv antibody can be used for pretargeting breast cancer for clinical diagnosis of patients; it also has potential for therapeutic applications.
Genetics and molecular research: GMR 03/2013; · 0.99 Impact Factor