Displaying publications 1 - 20 of 28 in total

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  1. Shrivastava G, Bakshi HA, Aljabali AA, Mishra V, Hakkim FL, Charbe NB, et al.
    Curr Drug Deliv, 2020;17(2):101-111.
    PMID: 31906837 DOI: 10.2174/1567201817666200106104332
    BACKGROUND: Nucleus targeted drug delivery provides several opportunities for the treatment of fatal diseases such as cancer. However, the complex nucleocytoplasmic barriers pose significant challenges for delivering a drug directly and efficiently into the nucleus. Aptamers representing singlestranded DNA and RNA qualify as next-generation highly advanced and personalized medicinal agents that successfully inhibit the expression of certain proteins; possess extraordinary gene-expression for manoeuvring the diseased cell's fate with negligible toxicity. In addition, the precisely directed aptamers to the site of action present a tremendous potential to reach the nucleus by escaping the ensuing barriers to exhibit a better drug activity and gene expression.

    OBJECTIVE: This review epigrammatically highlights the significance of targeted drug delivery and presents a comprehensive description of the principal barriers faced by the nucleus targeted drug delivery paradigm and ensuing complexities thereof. Eventually, the progress of nucleus targeting with nucleic acid aptamers and success achieved so far have also been reviewed.

    METHODS: Systematic literature search was conducted of research published to date in the field of nucleic acid aptamers.

    CONCLUSION: The review specifically points out the contribution of individual aptamers as the nucleustargeting agent rather than aptamers in conjugated form.

    Matched MeSH terms: Cell Nucleus/metabolism*
  2. Mohamed R, Lavin MF
    Biochem Biophys Res Commun, 1989 Feb 15;158(3):749-54.
    PMID: 2537634
    Anomalies in DNA replication, repair and recombination in ataxia-telangiectasia (A-T) point to a defect in structure or function of chromatin. In this study we have compared DNA-protein binding in nuclear extracts from control and A-T cells using two assay systems, filter-binding and DNA-accessibility. Interestingly, the extent of DNA protein binding over a range of protein concentration was significantly lower in A-T extracts. In addition the accessibility of the restriction enzyme Eco R1 to protein-bound plasmid was greater when A-T extracts were used. This is in keeping with the reduced binding observed in the filter-binding assay.
    Matched MeSH terms: Cell Nucleus/metabolism*
  3. Chen JE, Barbrook AC, Cui G, Howe CJ, Aranda M
    PLoS One, 2019;14(2):e0211936.
    PMID: 30779749 DOI: 10.1371/journal.pone.0211936
    Modern transformation and genome editing techniques have shown great success across a broad variety of organisms. However, no study of successfully applied genome editing has been reported in a dinoflagellate despite the first genetic transformation of Symbiodinium being published about 20 years ago. Using an array of different available transformation techniques, we attempted to transform Symbiodinium microadriaticum (CCMP2467), a dinoflagellate symbiont of reef-building corals, with the view to performing subsequent CRISPR-Cas9 mediated genome editing. Plasmid vectors designed for nuclear transformation containing the chloramphenicol resistance gene under the control of the CaMV p35S promoter as well as several putative endogenous promoters were used to test a variety of transformation techniques including biolistics, electroporation and agitation with silicon carbide whiskers. Chloroplast-targeted transformation was attempted using an engineered Symbiodinium chloroplast minicircle encoding a modified PsbA protein expected to confer atrazine resistance. We report that we have been unable to confer chloramphenicol or atrazine resistance on Symbiodinium microadriaticum strain CCMP2467.
    Matched MeSH terms: Cell Nucleus/metabolism
  4. Cheng KJ, Alshawsh MA, Mejia Mohamed EH, Thavagnanam S, Sinniah A, Ibrahim ZA
    Cell Oncol (Dordr), 2020 Apr;43(2):177-193.
    PMID: 31677065 DOI: 10.1007/s13402-019-00477-5
    BACKGROUND: In recent years, the high mobility group box-1 (HMGB1) protein, a damage-associated molecular pattern (DAMP) molecule, has been found to play multifunctional roles in the pathogenesis of colorectal cancer. Although much attention has been given to the diagnostic and prognostic values of HMGB1 in colorectal cancer, the exact functional roles of the protein as well as the mechanistic pathways involved have remained poorly defined. This systematic review aims to discuss what is currently known about the roles of HMGB1 in colorectal cancer development, growth and progression, and to highlight critical areas for future investigations. To achieve this, the bibliographic databases Pubmed, Scopus, Web of Science and ScienceDirect were systematically screened for articles from inception till June 2018, which address associations of HMGB1 with colorectal cancer.

    CONCLUSIONS: HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.

    Matched MeSH terms: Cell Nucleus/metabolism*
  5. Dasiman R, Rahman NS, Othman S, Mustafa MF, Yusoff NJ, Jusoff WH, et al.
    Med Sci Monit Basic Res, 2013 Oct 04;19:258-66.
    PMID: 24092420 DOI: 10.12659/MSMBR.884019
    BACKGROUND: This study aimed to investigate the effects of vitrification and slow freezing on actin, tubulin, and nuclei of in vivo preimplantation murine embryos at various developmental stages using a Confocal Laser Scanning Microscope (CLSM).

    MATERIAL/METHODS: Fifty female mice, aged 4-6 weeks, were used in this study. Animals were superovulated, cohabitated overnight, and sacrificed. Fallopian tubes were excised and flushed. Embryos at the 2-cell stage were collected and cultured to obtain 4- and 8-cell stages before being cryopreserved using vitrification and slow freezing. Fixed embryos were stained with fluorescence-labelled antibodies against actin and tubulin, as well as DAPI for staining the nucleus. Labelled embryos were scanned using CLSM and images were analyzed with Q-Win software V3.

    RESULTS: The fluorescence intensity of both vitrified and slow-frozen embryos was significantly lower for tubulin, actin, and nucleus as compared to non-cryopreserved embryos (p<0.001). Intensities of tubulin, actin, and nucleus in each stage were also decreased in vitrified and slow-frozen groups as compared to non-cryopreserved embryos.

    CONCLUSIONS: Cryopreservation of mouse embryos by slow freezing had a more detrimental effect on the actin, tubulin, and nucleus structure of the embryos compared to vitrification. Vitrification is therefore superior to slow freezing in terms of embryonic cryotolerance.

    Matched MeSH terms: Cell Nucleus/metabolism
  6. Al-batah MS, Isa NA, Klaib MF, Al-Betar MA
    Comput Math Methods Med, 2014;2014:181245.
    PMID: 24707316 DOI: 10.1155/2014/181245
    To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC)) to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE) algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS) is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy.
    Matched MeSH terms: Cell Nucleus/metabolism
  7. Fazalul Rahiman SS, Morgan M, Gray P, Shaw PN, Cabot PJ
    PLoS One, 2016;11(4):e0153005.
    PMID: 27055013 DOI: 10.1371/journal.pone.0153005
    Dynorphin 1-17, (DYN 1-17) opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP) receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1-17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) from lipopolysaccharide (LPS)-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1-17 and a specific range of fragments, with the greatest reduction observed with DYN 1-7 at a low concentration (10 nM). Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not other DYN 1-17 N-terminal fragments (DYN 1-10 and 1-11) on NF-κB/p65 nuclear translocation. DYN 1-17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1-7 at low concentrations (1 nM and 10 pM). These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1-17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways.
    Matched MeSH terms: Cell Nucleus/metabolism*
  8. Al-Shibli SM, Amjad NM, Al-Kubaisi MK, Mizan S
    Biochem Biophys Res Commun, 2017 Jan 22;482(4):1102-1106.
    PMID: 27914811 DOI: 10.1016/j.bbrc.2016.11.165
    Leptin (LEP) and leptin receptor (LEPR) have long been found associated with breast cancer. So far no high-resolution method such as electron microscopy has been used to investigate the subcellular localization of leptin and leptin receptor in breast cancer. We collected cancer and non-cancer breast tissues from 51 women with invasive ductal breast cancer. Leptin and leptin receptor in the tissues were estimated using immunohistochemistry (IHC). LEP and LEPR were localized at subcellular level by immunocytochemistry (ICC) using ultra-fine gold particle conjugated antibody, and visualized with transmission electron microscopy (TEM). IHC showed high presence of LEP and LEPR in 65% and 67% respectively of the breast cancer samples, 100% and 0% respectively of the adipose tissue samples, and no high presence in the non-cancer breast tissue samples. On TEM views both LEP and LEPR were found highly concentrated within the nucleus of the cancer cells, indicating that nucleus is the principal seat of action. However, presence of high concentration of LEP does not necessarily prove its over-expression, as often concluded, because LEP could be internalized from outside by LEPR in the cells. In contrast, LEPR is definitely over-expressed in the ductal breast cancer cells. Therefore, we hypothesize that over-expression of LEPR, rather than that of LEP has a fundamental role in breast carcinogenesis in particular, and probably for LEP-LEPR associated tumors in general.
    Matched MeSH terms: Cell Nucleus/metabolism
  9. Israf DA, Tham CL, Syahida A, Lajis NH, Sulaiman MR, Mohamad AS, et al.
    Phytomedicine, 2010 Aug;17(10):732-9.
    PMID: 20378317 DOI: 10.1016/j.phymed.2010.02.006
    In a previous communication we showed that atrovirinone, a 1,4-benzoquinone isolated from the roots of Garcinia atroviridis, was able to inhibit several major proinflammatory mediators of inflammation. In this report we show that atrovirinone inhibits NO and PGE(2) synthesis through inhibition of iNOS and COX-2 expression. We also show that atrovirinone inhibits the secretion of IL-1beta and IL-6 in a dose dependent fashion whereas the secretion of IL-10, the anti-inflammatory cytokine, was enhanced. Subsequently we determined that the inhibition of proinflammatory cytokine synthesis and inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation of p38 and ERK1/2. We also showed that atrovirinone prevented phosphorylation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation as demonstrated by expression analysis. We conclude that atrovirinone is a potential anti-inflammatory drug lead that targets both the MAPK and NF-kappaB pathway.
    Matched MeSH terms: Cell Nucleus/metabolism*
  10. Reena RM, Mastura M, Siti-Aishah MA, Munirah MA, Norlia A, Naqiyah I, et al.
    Ann Diagn Pathol, 2008 Oct;12(5):340-3.
    PMID: 18774496 DOI: 10.1016/j.anndiagpath.2008.04.001
    This is a study aimed to examine the distribution pattern of a specific minichromosome maintenance protein 2 (MCM2) in benign and malignant breast tissue. We also aim to correlate the frequency of expression of MCM2 with the degree of tumor differentiation. We used immunohistochemistry to examine the distribution and expression pattern of MCM2 on formalin-fixed paraffin-embedded tissue sections of benign (n = 30) and malignant breast tissue (n = 70) (IDC 56, DCIS 4, ILC 2, nonductal 4, mixed type 4). We quantified MCM2 expression by calculating a labeling index, which represents the percentage of epithelial nuclei that stained positively. Immunoreactivity was heterogenous in all the 70 malignant cases examined. Epithelial cells in cycle are most frequent at the tumor periphery. Labeling index of MCM2 was greatest in grade 3 (poorly differentiated) and lowest in grade 1 tumors (well differentiated). Minichromosome maintenance protein 2 expression in breast cancer showed a positive association with histologic grade (P < .05). In all the benign breast tissue examined, no proliferating compartments could be characterized. Minichromosome maintenance protein 2 is a useful proliferative marker of breast carcinoma. The frequency of expression of MCM2 showed an inverse correlation with the degree of tumor differentiation.
    Matched MeSH terms: Cell Nucleus/metabolism
  11. Khan S, Zakariah M, Palaniappan S
    Tumour Biol., 2016 Aug;37(8):10805-13.
    PMID: 26874727 DOI: 10.1007/s13277-016-4970-9
    Cancer has long been assumed to be a genetic disease. However, recent evidence supports the enigmatic connection of bacterial infection with the growth and development of various types of cancers. The cause and mechanism of the growth and development of prostate cancer due to Mycoplasma hominis remain unclear. Prostate cancer cells are infected and colonized by enteroinvasive M. hominis, which controls several factors that can affect prostate cancer growth in susceptible persons. We investigated M. hominis proteins targeting the nucleus of host cells and their implications in prostate cancer etiology. Many vital processes are controlled in the nucleus, where the proteins targeting M. hominis may have various potential implications. A total of 29/563 M. hominis proteins were predicted to target the nucleus of host cells. These include numerous proteins with the capability to alter normal growth activities. In conclusion, our results emphasize that various proteins of M. hominis targeted the nucleus of host cells and were involved in prostate cancer etiology through different mechanisms and strategies.
    Matched MeSH terms: Cell Nucleus/metabolism
  12. Khoo BY, Samian MR, Najimudin N, Tengku Muhammad TS
    PMID: 12524031
    The coding region of guinea pig peroxisome proliferator activated receptor gamma1 (gpPPARgamma1) cDNA was successfully cloned from adipose tissue by reverse transcription polymerase chain reaction (RT-PCR) using the designated primers based on the conserved regions of the other mammalian PPARgamma1 sequence. From RT-PCR, a combination of three cDNA fragments that comprised of the full length coding region PPARgamma1 cDNA gene were amplified, with the size of 498, 550 and 557 bp, respectively. All three fragments were then successfully assembled by utilising the internal restriction sites present at the overlapping regions to give rise to the full-length coding region of gpPPARgamma1 with the size of 1428 bp and consisting of 475 amino acids. Guinea pig PPARgamma1 is highly conserved with those of other species at protein and nucleotide levels. Gene expression studies showed that gpPPARgamma mRNA was predominantly expressed in adipose tissue followed by lung and spleen. However, at the protein level, PPARgamma was also found to be expressed in skeletal muscle.
    Matched MeSH terms: Cell Nucleus/metabolism
  13. Ting YH, Lu TJ, Johnson AW, Shie JT, Chen BR, Kumar S S, et al.
    J Biol Chem, 2017 Jan 13;292(2):585-596.
    PMID: 27913624 DOI: 10.1074/jbc.M116.747634
    Eukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins. Bcp1 has been shown to be necessary for the export of Mss4, a phosphatidylinositol 4-phosphate 5-kinase, and required for ribosome biogenesis. However, its specific function in ribosome biogenesis has not been described. Here, we show that Bcp1 dissociates Rpl23 from the karyopherins and associates with Rpl23 afterward. Loss of Bcp1 causes instability of Rpl23 and deficiency of 60S subunits. In summary, Bcp1 is a novel 60S biogenesis factor via chaperoning Rpl23 in the nucleus.
    Matched MeSH terms: Cell Nucleus/metabolism*
  14. Ng KL, Yap NY, Rajandram R, Small D, Pailoor J, Ong TA, et al.
    Pathology, 2018 Aug;50(5):511-518.
    PMID: 29935727 DOI: 10.1016/j.pathol.2018.03.003
    Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.
    Matched MeSH terms: Cell Nucleus/metabolism
  15. Lee YH, Pang SW, Poh CL, Tan KO
    J Cancer Res Clin Oncol, 2016 Sep;142(9):1967-77.
    PMID: 27424190 DOI: 10.1007/s00432-016-2205-5
    PURPOSE: Members of paraneoplastic Ma (PNMA) family have been identified as onconeuronal antigens, which aberrant expressions in cancer cells of patients with paraneoplastic disorder (PND) are closely linked to manifestation of auto-immunity, neuro-degeneration, and cancer. The purpose of present study was to determine the role of PNMA5 and its functional relationship to MOAP-1 (PNMA4) in human cancer cells.

    METHODS: PNMA5 mutants were generated through deletion or site-directed mutagenesis and transiently expressed in human cancer cell lines to investigate their role in apoptosis, subcellular localization, and potential interaction with MOAP-1 through apoptosis assays, fluorescence microscopy, and co-immunoprecipitation studies, respectively.

    RESULTS: Over-expressed human PNMA5 exhibited nuclear localization pattern in both MCF-7 and HeLa cells. Deletion mapping and mutagenesis studies showed that C-terminus of PNMA5 is responsible for nuclear localization, while the amino acid residues (391KRRR) within the C-terminus of PNMA5 are required for nuclear targeting. Deletion mapping and co-immunoprecipitation studies showed that PNMA5 interacts with MOAP-1 and N-terminal domain of PNMA5 is required for interaction with MOAP-1. Furthermore, co-expression of PNMA5 and MOAP-1 in MCF-7 cells significantly enhanced chemo-sensitivity of MCF-7 to Etoposide treatment, indicating that PNMA5 and MOAP-1 interact synergistically to promote apoptotic signaling in MCF-7 cells.

    CONCLUSIONS: Our results show that PNMA5 promotes apoptosis signaling in HeLa and MCF-7 cells and interacts synergistically with MOAP-1 through its N-terminal domain to promote apoptosis and chemo-sensitivity in human cancer cells. The C-terminal domain of PNMA5 is required for nuclear localization; however, both N-and C-terminal domains of PNMA5 appear to be required for pro-apoptotic function.

    Matched MeSH terms: Cell Nucleus/metabolism*
  16. Rostam MA, Shajimoon A, Kamato D, Mitra P, Piva TJ, Getachew R, et al.
    J. Pharmacol. Exp. Ther., 2018 04;365(1):156-164.
    PMID: 29438988 DOI: 10.1124/jpet.117.244483
    Transforming growth factor-β (TGF-β) is a pleiotropic growth factor implicated in the development of atherosclerosis for its role in mediating glycosaminoglycan (GAG) chain hyperelongation on the proteoglycan biglycan, a phenomenon that increases the binding of atherogenic lipoproteins in the vessel wall. Phosphorylation of the transcription factor Smad has emerged as a critical step in the signaling pathways that control the synthesis of biglycan, both the core protein and the GAG chains. We have used flavopiridol, a well-known cyclin-dependent kinase inhibitor, to study the role of linker region phosphorylation in the TGF-β-stimulated synthesis of biglycan. We used radiosulfate incorporation and SDS-PAGE to assess proteoglycan synthesis, real-time polymerase chain reaction to assess gene expression, and chromatin immunoprecipitation to assess the binding of Smads to the promoter region of GAG Synthesizing genes. Flavopiridol blocked TGF-β-stimulated synthesis of mRNA for the GAG synthesizing enzymes, and chondroitin 4-sulfotransferase (C4ST-1), chondroitin sulfate synthase-1 (ChSy-1) and TGF-β-mediated proteoglycans synthesis as well as GAG hyperelongation. Flavopiridol blocked TGF-β-stimulated Smad2 phosphorylation at both the serine triplet and the isolated threonine residue in the linker region. The binding of Smad to the promoter region of the C4ST-1 and ChSy-1 genes was stimulated by TGF-β, and this response was blocked by flavopiridol, demonstrating that linker region phosphorylated Smad can pass to the nucleus and positively regulate transcription. These results demonstrate the validity of the kinases, which phosphorylate the Smad linker region as potential therapeutic target(s) for the development of an agent to prevent atherosclerosis.
    Matched MeSH terms: Cell Nucleus/metabolism*
  17. Hussein SZ, Mohd Yusoff K, Makpol S, Mohd Yusof YA
    PLoS One, 2013;8(8):e72365.
    PMID: 24015236 DOI: 10.1371/journal.pone.0072365
    The activation of nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of a number of inflammatory diseases. In this study, we investigated the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via NF-κB signalling pathway. Rats paw edema was induced by subplantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey at different doses (1 or 2 g/kg, p.o.) and NSAID Indomethacin (10 mg/kg, p.o.), in two time points (1 and 7 days). Our results showed that Gelam honey at both concentrations suppressed the gene expressions of NF-κB (p65 & p50) and IκBα in inflamed rats paw tissues. In addition, Gelam honey inhibited the nuclear translocation and activation of NF-κB and decreased the cytosolic degradation of IκBα dose dependently in inflamed rats paw tissues. The immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-α were also decreased in inflamed rats paw tissues when treated with Gelam honey. The results of our findings suggest that Gelam honey exhibits its inhibitory effects by attenuating NF-κB translocation to the nucleus and inhibiting IκBα degradation, with subsequent decrease of inflammatory mediators COX-2 and TNF-α.
    Matched MeSH terms: Cell Nucleus/metabolism
  18. Lee ST, Wong PF, Cheah SC, Mustafa MR
    PLoS One, 2011;6(4):e18915.
    PMID: 21541327 DOI: 10.1371/journal.pone.0018915
    Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells.
    Matched MeSH terms: Cell Nucleus/metabolism
  19. Lee YH, Pang SW, Tan KO
    Biochem Biophys Res Commun, 2016 Apr 22;473(1):224-229.
    PMID: 27003254 DOI: 10.1016/j.bbrc.2016.03.083
    PNMA2, a member of the Paraneoplastic Ma Family (PNMA), was identified through expression cloning by using anti-sera from patients with paraneoplastic disorder. Tissue expression studies showed that PNMA2 was predominantly expressed in normal human brain; however, the protein was shown to exhibit abnormal expression profile as it was found to be expressed in a number of tumour tissues obtained from paraneopalstic patients. The abnormal expression profile of PNMA2 suggests that it might play an important role in tumorigenesis; however, apart from protein expression and immunological studies, the physiological role of PNMA2 remains unclear. In order to determine potential role of PNMA2 in tumorigenesis, and its functional relationship with PNMA family members, MOAP-1 (PNMA4) and PNMA1, expression constructs encoding the respective proteins were generated for both in vitro and in vivo studies. Our investigations showed that over-expressed MOAP-1 and PNMA1 promoted apoptosis and chemo-sensitization in MCF-7 cells as evidenced by condensed nuclei and Annexin-V positive MCF-7 cells; however, the effects mediated by these proteins were significantly inhibited or abolished when co-expressed with PNMA2 in MCF-7 cells. Furthermore, co-immunoprecipitation study showed that PNMA1 and MOAP-1 failed to associate with each other but readily formed respective heterodimer with PNMA2, suggesting that PNMA2 functions as antagonist of MOAP-1 and PNMA1 through heterodimeric interaction.
    Matched MeSH terms: Cell Nucleus/metabolism
  20. Nassar ZD, Aisha AF, Idris N, Khadeer Ahamed MB, Ismail Z, Abu-Salah KM, et al.
    Oncol Rep, 2012 Mar;27(3):727-33.
    PMID: 22134768 DOI: 10.3892/or.2011.1569
    Deregulated cell signaling pathways result in cancer development. More than one signal transduction pathway is involved in colorectal cancer pathogenesis and progression. Koetjapic acid (KA) is a naturally occurring seco-A-ring oleanene triterpene isolated from the Sandoricum koetjape stem bark. We report the cellular and molecular mechanisms of anticancer activity of KA towards human colorectal cancer. The results showed that KA induces apoptosis in HCT 116 colorectal carcinoma cells by inducing the activation of extrinsic and intrinsic caspases. We confirmed that KA-induced apoptosis was mediated by DNA fragmentation, nuclear condensation and disruption in the mitochondrial membrane potential. Further studies on the effect of KA on cancer pathways show that the compound causes down-regulation of Wnt, HIF-1α, MAP/ERK/JNK and Myc/Max signaling pathways and up-regulates the NF-κB signaling pathway. The result of this study highlights the anticancer potential of KA against colorectal cancer.
    Matched MeSH terms: Cell Nucleus/metabolism
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