Displaying publications 1 - 20 of 33 in total

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  1. Metastasis to the sinonasal tract from sigmoid colon adenocarcinoma
    bin Sabir Husin Athar PP, bte Ahmad Norhan N, bin Saim L, bin Md Rose I, bte Ramli R
    Ann Acad Med Singap, 2008 Sep;37(9):788-3.
    PMID: 18989497
    INTRODUCTION: Metastatic adenocarcinoma from the gastrointestinal tract to the sinonasal tract is rare. The histological morphology of this lesion is indistinguishable from the colonic variant of primary sinus adenocarcinoma or intestinal-type adenocarcinoma (ITAC).

    CLINICAL PICTURE: This is a report of a case of metastatic adenocarcinoma of colorectal origin to the paranasal sinuses in a 52-year-old female who was previously treated for adenocarcinoma of the sigmoid colon. A histologic study of the surgical specimen from the sinonasal cavity demonstrated a tumour identical to the patient's prior primary tumour of the colon. The sinonasal neoplastic tissue showed marked positivity for carcinoembryonic antigen and expressed cytokeratin 20, which differentiates metastatic colonic adenocarcinoma from ITAC.

    TREATMENT/OUTCOME: The patient received palliative radiation but died 3 months after the diagnosis.

    CONCLUSION: Distinguishing metastatic adenocarcinoma from gastrointestinal tract from ITAC can be difficult. In view of the resemblance, immunohistochemical staining can help in differentiating them. It is important to recognise these as metastatic lesions as the treatment is mainly palliative.

    Matched MeSH terms: Adenocarcinoma/metabolism
  2. Fulltext Cytotoxicity and apoptotic activities of alpha-, gamma- and delta-tocotrienol isomers on human cancer cells
    Lim SW, Loh HS, Ting KN, Bradshaw TD, Zeenathul NA
    BMC Complement Altern Med, 2014;14:469.
    PMID: 25480449 DOI: 10.1186/1472-6882-14-469
    Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched.
    Matched MeSH terms: Adenocarcinoma/metabolism
  3. Fulltext In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans
    Liew KL, Jee JM, Yap I, Yong PV
    PLoS One, 2016;11(4):e0153356.
    PMID: 27054608 DOI: 10.1371/journal.pone.0153356
    Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection.
    Matched MeSH terms: Adenocarcinoma/metabolism*
  4. Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment
    Bose A, Elyagoby A, Wong TW
    Int J Pharm, 2014 Jul 1;468(1-2):178-86.
    PMID: 24709212 DOI: 10.1016/j.ijpharm.2014.04.006
    In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.
    Matched MeSH terms: Adenocarcinoma/metabolism
  5. Fulltext Potential activity of fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. seeds as estrogen receptor antagonist based on cytotoxicity and molecular modelling studies
    Muchtaridi M, Yusuf M, Diantini A, Choi SB, Al-Najjar BO, Manurung JV, et al.
    Int J Mol Sci, 2014 Apr 25;15(5):7225-49.
    PMID: 24776765 DOI: 10.3390/ijms15057225
    Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 µM. At 11.2 µM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.
    Matched MeSH terms: Adenocarcinoma/metabolism
  6. Fulltext Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues
    Othman EQ, Kaur G, Mutee AF, Muhammad TS, Tan ML
    J Clin Lab Anal, 2009;23(4):249-58.
    PMID: 19623642 DOI: 10.1002/jcla.20309
    Autophagy is a protein degradation process within the cell and its deregulation has been linked to various diseases and the formation of cancer. One of the important proteins involved in the autophagy process is microtubule-associated protein 1 light chain 3 (MAP1LC3). The aims of this study were to determine the MAP1LC3A and MAP1LC3B protein expression in both normal and cancer breast tissues and to determine the relationship between the expression of these proteins and type of tissues. Immunohistochemistry assessments were carried out on tissue microarrays consisting of breast tissues. MAP1LC3A expression was detected in 52/56 of normal breast tissue cores and 65/67 of breast cancer tissue cores. MAP1LC3B expression was detected in 55/56 of normal breast tissue cores and 67/67 of breast cancer tissue cores. MAP1LC3A and MAP1LC3B protein are expressed in the majority of normal and cancer breast tissues. A large number of MAP1LC3A and MAP1LC3B positive breast cancer tissues cores have high proportion of stained cells (81-100%) as compared with normal breast tissues. However, a significantly higher number of breast cancer tissues were found to express the MAP1LC3A protein with strong immunoreactivity as compared with the normal tissues, suggesting that MAP1LC3A may play a role in breast cancer development.
    Matched MeSH terms: Adenocarcinoma/metabolism*
  7. Fulltext Highly pathogenic avian influenza virus nucleoprotein interacts with TREX complex adaptor protein Aly/REF
    Balasubramaniam VR, Hong Wai T, Ario Tejo B, Omar AR, Syed Hassan S
    PLoS One, 2013;8(9):e72429.
    PMID: 24073193 DOI: 10.1371/journal.pone.0072429
    We constructed a novel chicken (Gallus gallus) lung cDNA library fused inside yeast acting domain vector (pGADT7). Using yeast two-hybrid screening with highly pathogenic avian influenza (HPAI) nucleoprotein (NP) from the strain (A/chicken/Malaysia/5858/2004(H5N1)) as bait, and the Gallus gallus lung cDNA library as prey, a novel interaction between the Gallus gallus cellular RNA export adaptor protein Aly/REF and the viral NP was identified. This interaction was confirmed and validated with mammalian two hybrid studies and co-immunoprecipitation assay. Cellular localization studies using confocal microscopy showed that NP and Aly/REF co-localize primarily in the nucleus. Further investigations by mammalian two hybrid studies into the binding of NP of other subtypes of influenza virus such as the swine A/New Jersey/1976/H1N1 and pandemic A/Malaysia/854/2009(H1N1) to human Aly/REF, also showed that the NP of these viruses interacts with human Aly/REF. Our findings are also supported by docking studies which showed tight and favorable binding between H5N1 NP and human Aly/REF, using crystal structures from Protein Data Bank. siRNA knockdown of Aly/REF had little effect on the export of HPAI NP and other viral RNA as it showed no significant reduction in virus titer. However, UAP56, another component of the TREX complex, which recruits Aly/REF to mRNA was found to interact even better with H5N1 NP through molecular docking studies. Both these proteins also co-localizes in the nucleus at early infection similar to Aly/REF. Intriguingly, knockdown of UAP56 in A549 infected cells shows significant reduction in viral titer (close to 10 fold reduction). Conclusively, our study have opened new avenues for research of other cellular RNA export adaptors crucial in aiding viral RNA export such as the SRSF3, 9G8 and ASF/SF2 that may play role in influenza virus RNA nucleocytoplasmic transport.
    Matched MeSH terms: Adenocarcinoma/metabolism*
  8. Analysis of differentially expressed proteins in cancerous and normal colonic tissues
    Gam LH, Leow CH, Man CN, Gooi BH, Singh M
    World J Gastroenterol, 2006 Aug 21;12(31):4973-80.
    PMID: 16937492
    AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.

    METHODS: Colon tissues (normal and cancerous) were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.

    RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.

    CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.

    Matched MeSH terms: Adenocarcinoma/metabolism
  9. Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: synthesis and evaluation of lantadene congeners
    Suthar SK, Boon HL, Sharma M
    Eur J Med Chem, 2014 Mar 3;74:135-44.
    PMID: 24457265 DOI: 10.1016/j.ejmech.2013.12.052
    The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22β-hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 μmol, respectively against TNF-α induced activation of NF-κB. The congeners 12 and 13 exhibited inhibition of IKKβ in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 μmol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties.
    Matched MeSH terms: Adenocarcinoma/metabolism
  10. Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation
    Monika, Sharma A, Suthar SK, Aggarwal V, Lee HB, Sharma M
    Bioorg Med Chem Lett, 2014 Aug 15;24(16):3814-8.
    PMID: 25027934 DOI: 10.1016/j.bmcl.2014.06.068
    The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.
    Matched MeSH terms: Adenocarcinoma/metabolism
  11. Minichromosome maintenance protein 2 is a reliable proliferative marker in breast carcinoma
    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: Adenocarcinoma/metabolism*
  12. γ-Synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to the colon adenocarcinoma LS 174T cell line
    Goh KW, Say YH
    Tumour Biol., 2015 Sep;36(10):7947-60.
    PMID: 25956278 DOI: 10.1007/s13277-015-3455-6
    γ-synuclein, a neuronal protein of the synuclein family, is involved in carcinogenesis. To investigate its role in colorectal cancer carcinogenesis, we overexpressed γ-synuclein in LS 174T colon adenocarcinoma cell line (termed LS 174T-γsyn). When compared with untransfected/mock transfectants, LS 174T-γsyn had higher mobility in scratch wound assay, tend to scatter more in cell-scattering assay, and had enhanced lamellipodia and filopodia formation in cell-spreading assay. Enhanced adhesion of LS 174T-γsyn to fibronectin and collagen and significantly higher proliferation rate showed that γ-synuclein was able to increase extracellular matrix interaction and promoted proliferation of LS 174T. Higher invasiveness of LS 174T-γsyn was evidenced by enhanced invasion to the bottom of the basement membrane in Boyden chamber assay. However, LS 174T-γsyn were significantly more vulnerable to doxorubicin, vincristine and hydrogen peroxide insults, via apoptotic cell death. LS 174T-γsyn also had reduced anchorage-independent growth as shown by reduced colony formation and reduced anoikis resistance. We found that overexpression of γ-synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to LS 174T, where the former was mediated through enhanced cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation, while the latter involved hepatocyte growth factor (HGF) downregulation and subsequent downstream signalling pathways possibly involving extracellular signal-regulated kinases (ERK)1/2, p38α, c-Jun N-terminal kinase (JNK) pan and Signal Transducers and Activators of Transcription (STATs). This unexpected contrasting finding as compared to other similar studies on colon cancer cell lines might be correlated with the degree of tumour advancement from which the cell lines were derived from.
    Matched MeSH terms: Adenocarcinoma/metabolism
  13. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: characterization, stability assessment and cytotoxicity
    How CW, Rasedee A, Manickam S, Rosli R
    Colloids Surf B Biointerfaces, 2013 Dec 1;112:393-9.
    PMID: 24036474 DOI: 10.1016/j.colsurfb.2013.08.009
    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.
    Matched MeSH terms: Adenocarcinoma/metabolism
  14. Alterations in mucin type: an indicator for suspicion of malignant gastric transformation
    Cheah PL, Ramachandran K
    Malays J Pathol, 1994 Jun;16(1):39-42.
    PMID: 16329574
    Mucins are produced by both benign and malignant gastric epithelium. In general, mucins can be classified into neutral and acidic mucins. The latter are of 2 major types, sulphated (sulphomucins) and carboxylated (sialomucins). A retrospective study was initiated at the Department of Pathology, University Hospital, Kuala Lumpur to histochemically study the mucin profiles of cases of intestinal (IGC) and diffuse (DGC) types of gastric carcinoma in Malaysian patients to determine whether a significant change of mucin type occurs in the event of malignant transformation. 42 IGC and 37 DGC were subjected to alcian blue-periodic acid Schiff and high iron diamine-alcian blue histochemical staining. In addition, 18 cases of gastrectomies performed for benign lesions in the stomach served as normal controls. The number of cases of IGC and DGC which exhibited sulphomucin production was significantly increased (p < 0.001) compared to normal controls. Also, the number of cases of DGC which produced neutral mucin were significantly less (p < 0.05) than the control group. However, there was no significant difference between the number of IGC and DGC cases which demonstrated sialomucin production and normal controls. It appears that while not pathognomonic, a lack of neutral mucin production should alert the pathologist to the possibility of a gastric malignancy, in particular DGC. The likelihood of a malignant lesion would be further supported if there is an increased sulphomucin production.
    Matched MeSH terms: Adenocarcinoma/metabolism
  15. Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture model
    Elendran S, Muniyandy S, Lee WW, Palanisamy UD
    Food Funct, 2019 Feb 20;10(2):602-615.
    PMID: 30566155 DOI: 10.1039/c8fo01927d
    Ellagitannins, found abundantly in berries, pomegranates, walnuts and almonds, have been increasingly investigated for their health benefits. Geraniin (GE), an ellagitannin, found predominantly in herbal plants, as well has been shown to exhibit a number of biological activities. Like many hydrolysable tannins, geraniin is water-soluble and readily undergoes hydrolysis in the presence of hot water, weak acids and weak bases to yield several metabolites including corilagin (CO), ellagic acid (EA) and gallic acid (GA). There are numerous studies on the pharmacological effectiveness of GE, CO and GA. However, the intestinal permeability of GE and CO has never been investigated before. Caco-2 cell transport assay was utilized to evaluate the in vitro permeability of GE and its metabolites. GE, CO and EA were found to have no apparent permeability (Papp) while GA displayed a Papp value of 31.3 ± 1.1 × 10-6 cm s-1. Mass balance studies showed a loss of geraniin and its metabolites during transport. Chemical stability studies in the transport buffers revealed that GE and CO were hydrolyzed in the HBSS buffers. Experiments using lysed cells revealed that GE and its metabolites were metabolized during transport. Absorption and desorption studies confirmed the accumulation of EA inside the cells. The above results indicate that the compounds have poor oral absorption. To consider these compounds or their natural extracts as oral nutraceutical candidates, formulation strategies are mandatory.
    Matched MeSH terms: Adenocarcinoma/metabolism*
  16. Fulltext Clinicopathological comparison of adenocarcinoma of cervix and endometrium using cell cycle markers: P16ink4a, P21waf1, and p27Kip1 on 132 cancers
    Abu Backer FM, Nik Mustapha NR, Othman NH
    Infect Dis Obstet Gynecol, 2011;2011:857851.
    PMID: 22114462 DOI: 10.1155/2011/857851
    We studied the clinicopathological parameters of adenocarcinoma arising from endocervix (ECA) and from endometrium (EMA) based on the expression of P16ink4a, P21waf1, and p27Kip1 proteins.
    Matched MeSH terms: Adenocarcinoma/metabolism*
  17. Modulation of cell growth and PPARgamma expression in human colorectal cancer cell lines by ciglitazone
    Yaacob NS, Darus HM, Norazmi MN
    Exp. Toxicol. Pathol., 2008 Sep;60(6):505-12.
    PMID: 18579355 DOI: 10.1016/j.etp.2008.05.006
    Studies have shown that ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) can induce differentiation and inhibit proliferation of several cancer cells. The present study was performed to investigate the effects of the PPARgamma ligand, ciglitazone, and the involvement of PPARgamma in modulating the growth of human colorectal cancer cells. Lactate dehydrogenase release assay showed that ciglitazone potently inhibited HT-29 (well-differentiated) and COLO-205 (poorly differentiated) colorectal adenocarcinoma cell growth. Measurement of apoptosis by flow cytometry using a fluorescein-conjugated monoclonal antibody against cytokeratin 18 revealed a high induction of apoptosis by ciglitazone in a time-dependent fashion. The expression of PPARgamma1 but not PPARgamma2 mRNA was significantly downregulated as measured by real-time quantitative PCR, and the PPARgamma protein levels were decreased as determined by Western blot analysis. We conclude that ciglitazone treatment suppressed colon cancer cell growth via induction of apoptosis. However, the anticancer effects of ciglitazone may not depend solely on PPARgamma activation.
    Matched MeSH terms: Adenocarcinoma/metabolism
  18. Fulltext Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells
    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: Adenocarcinoma/metabolism*
  19. Fulltext Alpha-tomatine attenuation of in vivo growth of subcutaneous and orthotopic xenograft tumors of human prostate carcinoma PC-3 cells is accompanied by inactivation of nuclear factor-kappa B signaling
    Lee ST, Wong PF, He H, Hooper JD, Mustafa MR
    PLoS One, 2013;8(2):e57708.
    PMID: 23437404 DOI: 10.1371/journal.pone.0057708
    Nuclear factor-kappa B (NF-κB) plays a role in prostate cancer and agents that suppress its activation may inhibit development or progression of this malignancy. Alpha (α)-tomatine is the major saponin present in tomato (Lycopersicon esculentum) and we have previously reported that it suppresses tumor necrosis factor-alpha (TNF-α)-induced nuclear translocation of nuclear factor-kappa B (NF-κB) in androgen-independent prostate cancer PC-3 cells and also potently induces apoptosis of these cells. However, the precise mechanism by which α-tomatine suppresses NF-κB nuclear translocation is yet to be elucidated and the anti-tumor activity of this agent in vivo has not been examined.
    Matched MeSH terms: Adenocarcinoma/metabolism
  20. Fulltext (6E,10E) Isopolycerasoidol and (6E,10E) Isopolycerasoidol Methyl Ester, Prenylated Benzopyran Derivatives from Pseuduvaria monticola Induce Mitochondrial-Mediated Apoptosis in Human Breast Adenocarcinoma Cells
    Taha H, Looi CY, Arya A, Wong WF, Yap LF, Hasanpourghadi M, et al.
    PLoS One, 2015;10(5):e0126126.
    PMID: 25946039 DOI: 10.1371/journal.pone.0126126
    Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.
    Matched MeSH terms: Adenocarcinoma/metabolism
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