Displaying publications 1 - 20 of 606 in total

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  1. Jabbarzadeh Kaboli P, Rahmat A, Ismail P, Ling KH
    Eur J Pharmacol, 2014 Oct 5;740:584-95.
    PMID: 24973693 DOI: 10.1016/j.ejphar.2014.06.025
    Breast cancer is the most common cancer among women worldwide and novel therapeutic agents are needed to treat this disease. The plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors. This review will discuss recent studies and consider the application of new prospective approaches based on microRNAs and other crucial regulators for use in future studies to define the action of berberine in cancer. The effects of berberine on cancer cell survival and proliferation are also outlined.
    Matched MeSH terms: Neoplasms/metabolism
  2. Hasanpourghadi M, Looi CY, Pandurangan AK, Sethi G, Wong WF, Mustafa MR
    Curr Drug Targets, 2017;18(9):1086-1094.
    PMID: 27033190 DOI: 10.2174/1389450117666160401124842
    Phytometabolites are functional elements derived from plants and most of them exhibit therapeutic characteristics such as anti-cancer, anti-inflammatory and anti-oxidant effects. Phytometabolites exert their anti-cancer effect by targeting multiple signaling pathways. One of the remarkable phenomena targeted by phytometabolites is the Warburg effect. The Warburg effect describes the observation that cancer cells exhibit an increased rate of glycolysis and aberrant redox activity compared to normal cells. This phenomenon promotes further cancer development and progression. Recent observations revealed that some phytometabolites could target metabolic-related enzymes (e.g. Hexokinase, Pyruvate kinase M2, HIF-1) in cancer cells, with little or no harm to normal cells. Since hyper-proliferation of cancer cells is fueled by higher cellular metabolism, phytometabolites targeting these metabolic pathways can create synergistic crosstalk with induced apoptotic pathways and sensitize cancer cells to chemotherapeutic agents. In this review, we discuss phytometabolites that target the Warburg effect and the underlying molecular mechanism that leads to tumor growth suppression.
    Matched MeSH terms: Neoplasms/metabolism*
  3. Mohd Khair SZN, Abd Radzak SM, Mohamed Yusoff AA
    Dis Markers, 2021;2021:7675269.
    PMID: 34326906 DOI: 10.1155/2021/7675269
    Cancer is a heterogeneous group of diseases, the progression of which demands an accumulation of genetic mutations and epigenetic alterations of the human nuclear genome or possibly in the mitochondrial genome as well. Despite modern diagnostic and therapeutic approaches to battle cancer, there are still serious concerns about the increase in death from cancer globally. Recently, a growing number of researchers have extensively focused on the burgeoning area of biomarkers development research, especially in noninvasive early cancer detection. Intergenomic cross talk has triggered researchers to expand their studies from nuclear genome-based cancer researches, shifting into the mitochondria-mediated associations with carcinogenesis. Thus, it leads to the discoveries of established and potential mitochondrial biomarkers with high specificity and sensitivity. The research field of mitochondrial DNA (mtDNA) biomarkers has the great potential to confer vast benefits for cancer therapeutics and patients in the future. This review seeks to summarize the comprehensive insights of nuclear genome cancer biomarkers and their usage in clinical practices, the intergenomic cross talk researches that linked mitochondrial dysfunction to carcinogenesis, and the current progress of mitochondrial cancer biomarker studies and development.
    Matched MeSH terms: Neoplasms/metabolism*
  4. Ching-Shian Leong V, Jabal MF, Leong PP, Abdullah MA, Gul YA, Seow HF
    Cancer Genet. Cytogenet., 2008 Dec;187(2):74-9.
    PMID: 19027487 DOI: 10.1016/j.cancergencyto.2008.07.005
    Somatic mutations of phosphoinositide-3-kinase, catalytic, alpha; PIK3CA gene have been reported in several types of human cancers. The majority of the PIK3CA mutations map to the three "hot spots" - E542 K and E545 K in the helical (exon 9) and H1047R in the kinase (exon 20) domains of the p110alpha. These hot spot mutations lead to a gain of function in PI3 K signaling. We aimed to determine the frequency of PIK3CA mutations in the three most common Malaysian cancers. In this study, we assessed the genetic alterations in the PIK3CA gene in a series of 20 breast carcinomas, 24 colorectal carcinomas, 27 nasopharyngeal carcinomas (NPC), and 5 NPC cell lines. We performed mutation analysis of the PIK3CA gene by genomic polymerase chain reaction (PCR) and followed by DNA direct sequencing in exons 9 and 20. No mutations were detected in any of the 24 colorectal and 27 NPC samples, but one hot spot mutation located at exon 20 was found in a NPC cell line, SUNE1. Interestingly, PIK3CA somatic mutations were present in 6/20 (30%) breast carcinomas. Two of the six mutations, H1047R, have been reported previously as a hot spot mutation. Only one out of three hot spot mutations were identified in breast tumor samples. The remaining four mutations were novel. Our data showed that a higher incidence rate of PIK3CA mutations was present in Malaysian breast cancers as compared to colorectal and nasopharyngeal tumor tissues. Our findings also indicate that PIK3CA mutations play a pivotal role in activation of the PI3 K signaling pathway in breast cancer, and specific inhibitors of PIK3CA could be useful for breast cancer treatment in Malaysia.
    Matched MeSH terms: Breast Neoplasms/metabolism; Nasopharyngeal Neoplasms/metabolism; Colorectal Neoplasms/metabolism
  5. Yap YH, Say YH
    Cell Biol Int, 2012 Mar 1;36(3):273-7.
    PMID: 21980981 DOI: 10.1042/CBI20110088
    Since the discovery of PrPC (cellular prion protein), most studies have focused on its role in neurodegenerative diseases, whereas its function outside the nervous system remains obscure. We investigated the ability of PrPC in resisting TNFα (tumour necrosis factor α) apoptosis in three PrPC-transiently transfected cancer cell lines, renal adenocarcinoma ACHN, oral squamous cell carcinoma HSC-2 and colon adenocarcinoma LS174T. PrPC-expressing ACHN and LS174T cells had higher viabilities compared with the mock-transfected cells, while the transient overexpression of PrPC had minimal overall effect on HSC-2 cells due to its high endogenous PrPC expression. Cell cycles were also analysed, with both PrPC expressing ACHN and LS174T cells having a significantly higher proliferative index than mock-transfected cells. Flow cytometry analysis indicated a G1/S-phase cell cycle transition in both PrPC-expressing ACHN and LS174T cells. PrPC resists TNFα apoptosis due to a modest, but statistically significant, cell-specific cytoprotection compared with mock-transfected cells.
    Matched MeSH terms: Colonic Neoplasms/metabolism*; Kidney Neoplasms/metabolism*; Mouth Neoplasms/metabolism*
  6. Erejuwa OO, Sulaiman SA, Ab Wahab MS
    Oxid Med Cell Longev, 2013;2013:931251.
    PMID: 24369491 DOI: 10.1155/2013/931251
    Cancer cells generate reactive oxygen species (ROS) resulting from mitochondrial dysfunction, stimulation of oncogenes, abnormal metabolism, and aggravated inflammatory activities. Available evidence also suggests that cancer cells depend on intrinsic ROS level for proliferation and survival. Both physiological and pathophysiological roles have been ascribed to ROS which cause lipid peroxidation. In spite of their injurious effects, the ROS and the resulting lipid peroxidation products could be beneficial in cancer treatment. This review presents research findings suggesting that ROS and the resulting lipid peroxidation products could be utilized to inhibit cancer growth or induce cancer cell death. It also underscores the potential of lipid peroxidation products to potentiate the antitumor effect of other anticancer agents. The review also highlights evidence demonstrating other potential applications of lipid peroxidation products in cancer treatment. These include the prospect of lipid peroxidation products as a diagnostic tool to predict the chances of cancer recurrence, to monitor treatment progress or how well cancer patients respond to therapy. Further and detailed research is required on how best to successfully, effectively, and selectively target cancer cells in humans using lipid peroxidation products. This may prove to be an important strategy to complement current treatment regimens for cancer patients.
    Matched MeSH terms: Neoplasms/metabolism*
  7. Mohamed E, Abdul-Rahman PS, Doustjalali SR, Chen Y, Lim BK, Omar SZ, et al.
    Electrophoresis, 2008 Jun;29(12):2645-50.
    PMID: 18494030 DOI: 10.1002/elps.200700828
    A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O-glycosylated fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.
    Matched MeSH terms: Bone Neoplasms/metabolism; Breast Neoplasms/metabolism; Nasopharyngeal Neoplasms/metabolism; Ovarian Neoplasms/metabolism
  8. Lai LC, Cheong SK, Goh KL, Leong CF, Loh CS, Lopez JB, et al.
    Malays J Pathol, 2003 Dec;25(2):83-105.
    PMID: 16196365
    Tumour markers are substances related to the presence or progress of a tumour. An ideal tumour marker is (1) detectable only when malignancy is present, (2) specific for the type and site of malignancy, (3) correlates with the amount of malignant tissue present and (4) responds rapidly to a change in tumour size. At present, no tumour marker fulfills all of the above criteria. The first part of the review discusses the clinical usefulness of the commonly requested serum tumour markers, namely, prostate-specific antigen (PSA), CA 19-9, carcinoembryonic antigen (CEA), CA 125, CA 15-3, human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). It is hoped that this review article will decrease the abuse and misuse of these commonly requested serum tumour markers. The second part of the review discusses the clinical usefulness of catecholamines and their metabolites, calcitonin, thyroglobulin, parathyroid hormone, prolactin, adrenocorticotrophic hormone, oestrogen and progesterone receptors, p53, HER-2/c-erbB2, BRCA1 and BRCA2.
    Matched MeSH terms: Neoplasms/metabolism
  9. Nakkarach A, Foo HL, Song AA, Mutalib NEA, Nitisinprasert S, Withayagiat U
    Microb Cell Fact, 2021 Feb 05;20(1):36.
    PMID: 33546705 DOI: 10.1186/s12934-020-01477-z
    BACKGROUND: Extracellular metabolites of short chain fatty acids (SCFA) excreted by gut microbiota have been reported to play an important role in the regulation of intestinal homeostasis. Apart from supplying energy, SCFA also elicit immune stimulation in animal and human cells. Therefore, an attempt was conducted to isolate SCFA producing bacteria from healthy human microbiota. The anti-cancer and anti-inflammatory effects of extracellular metabolites and individual SFCA were further investigated by using breast, colon cancer and macrophage cells. Toxin, inflammatory and anti-inflammatory cytokine gene expressions were investigated by RT-qPCR analyses in this study.

    RESULTS: Escherichia coli KUB-36 was selected in this study since it has the capability to produce seven SCFA extracellularly. It produced acetic acid as the main SCFA. It is a non-exotoxin producer and hence, it is a safe gut microbiota. The IC50 values indicated that the E. coli KUB-36 metabolites treatment elicited more potent cytotoxicity effect on MCF7 breast cancer cell as compared to colon cancer and leukemia cancer cells but exhibited little cytotoxic effects on normal breast cell. Furthermore, E. coli KUB-36 metabolites and individual SCFA could affect inflammatory responses in lipopolysaccharide-induced THP-1 macrophage cells since they suppressed inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α well as compared to the control, whilst inducing anti-inflammatory cytokine IL-10 expression.

    CONCLUSION: SCFA producing E. coli KUB-36 possessed vast potential as a beneficial gut microbe since it is a non-exotoxin producer that exhibited beneficial cytotoxic effects on cancer cells and elicited anti-inflammatory activity simultaneously. However, the probiotic characteristic of E. coli KUB-36 should be further elucidated using in vivo animal models.

    Matched MeSH terms: Neoplasms/metabolism
  10. Briggs MT, Condina MR, Klingler-Hoffmann M, Arentz G, Everest-Dass AV, Kaur G, et al.
    Proteomics Clin Appl, 2019 05;13(3):e1800099.
    PMID: 30367710 DOI: 10.1002/prca.201800099
    Protein glycosylation, particularly N-linked glycosylation, is a complex posttranslational modification (PTM), which plays an important role in protein folding and conformation, regulating protein stability and activity, cell-cell interaction, and cell signaling pathways. This review focuses on analytical techniques, primarily MS-based techniques, to qualitatively and quantitatively assess N-glycosylation while successfully characterizing compositional, structural, and linkage features with high specificity and sensitivity. The analytical techniques explored in this review include LC-ESI-MS/MS and MALDI time-of-flight MS (MALDI-TOF-MS), which have been used to analyze clinical samples, such as serum, plasma, ascites, and tissue. Targeting the aberrant N-glycosylation patterns observed in MALDI-MS imaging (MSI) offers a platform to visualize N-glycans in tissue-specific regions. The studies on the intra-patient (i.e., a comparison of tissue-specific regions from the same patient) and inter-patient (i.e., a comparison of tissue-specific regions between different patients) variation of early- and late-stage ovarian cancer (OC) patients identify specific N-glycan differences that improve understanding of the tumor microenvironment and potentially improve therapeutic strategies for the clinic.
    Matched MeSH terms: Ovarian Neoplasms/metabolism*
  11. Khor ES, Noor SM, Wong PF
    In Vivo, 2019 10 31;33(6):1713-1720.
    PMID: 31662495 DOI: 10.21873/invivo.11661
    The mammalian target of rapamycin (mTOR), a 289 kDa serine/threonine protein kinase of the phosphoinositide 3-kinase (PI3K)-related family is known for its role in regulating lifespan and the aging process in humans and rodents. Aging in zebrafish very much resembles aging in humans. Aged zebrafish often manifest with spinal curvature, cataracts and cognitive frailty, akin to human age-related phenotypical effects such as osteoarthritis, dwindling vision and cognitive dysfunction. However, the role of the zebrafish orthologue of mTOR, ztor, is less defined in these areas. This review paper discusses the tale of growing old in the zebrafish, the physiological roles of ztor in normal developmental processes and its involvement in the pathogenesis of aging-related diseases such as metabolic disorders and cancers.
    Matched MeSH terms: Neoplasms/metabolism
  12. Mohammad SIS, Vasudevan A, Enwa FO, Bansal J, Chahar M, Eldesoqui M, et al.
    Med Oncol, 2024 Sep 11;41(10):244.
    PMID: 39259412 DOI: 10.1007/s12032-024-02494-3
    The likelihood of survival for cancer patients has greatly improved due to chemotherapy medicines. However, these antitumor agents might also have unfavorable effects on the cardiovascular system, which could result in sudden or gradual cardiac failure. The production of free radicals that result in oxidative stress appears to be the key mechanism by which chemotherapy-induced cardiotoxicity (CIC) happens. Reports suggest that the Sirtuin-1 (Sirt1)/Nuclear factor E2-associated factor 2 (Nrf2) signaling pathway has been considered an alternative path for counteracting cardiotoxicity by suppressing oxidative stress, inflammation, and apoptosis. This review concludes recent knowledge about CIC with a special focus on the anti-oxidative regulation properties of the Sirt1/Nrf2 pathway.
    Matched MeSH terms: Neoplasms/metabolism
  13. Pawar S, Liew TO, Stanam A, Lahiri C
    Chem Biol Drug Des, 2020 09;96(3):995-1004.
    PMID: 32410355 DOI: 10.1111/cbdd.13672
    Biomarkers can offer great promise for improving prevention and treatment of complex diseases such as cancer, cardiovascular diseases, and diabetes. These can be used as either diagnostic or predictive or as prognostic biomarkers. The revolution brought about in biological big data analytics by artificial intelligence (AI) has the potential to identify a broader range of genetic differences and support the generation of more robust biomarkers in medicine. AI is invigorating biomarker research on various fronts, right from the cataloguing of key mutations driving the complex diseases like cancer to the elucidation of molecular networks underlying diseases. In this study, we have explored the potential of AI through machine learning approaches to propose that these methods can act as recommendation systems to sort and prioritize important genes and finally predict the presence of specific biomarkers. Essentially, we have utilized microarray datasets from open-source databases, like GEO, for breast, lung, colon, and ovarian cancer. In this context, different clustering analyses like hierarchical and k-means along with random forest algorithm have been utilized to classify important genes from a pool of several thousand genes. To this end, network centrality and pathway analysis have been implemented to identify the most potential target as CREB1.
    Matched MeSH terms: Breast Neoplasms/metabolism*; Ovarian Neoplasms/metabolism*
  14. Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC
    J Vet Sci, 2018 Mar 31;19(2):162-171.
    PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162
    MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.
    Matched MeSH terms: Breast Neoplasms/metabolism; Neoplasms/metabolism*
  15. Pan Y, Ong EC
    Xenobiotica, 2017 Oct;47(10):923-932.
    PMID: 27690753 DOI: 10.1080/00498254.2016.1244370
    1. This article aims to evaluate the potentials of using cytochrome P450 2W1 (CYP2W1) as a biomarker and a drug target of cancer because of its characteristic cancer-specific expression. 2. Discrepant findings comparing the expression levels of CYP2W1 in cancer and non-cancer samples were reported. In general, the expression followed a developmental pattern. The demethylation status of CpG island and the expression levels of CYP2W1 genes was positively correlated. 3. CYP2W1 was able to activate several procarcinogens, anticancer pro-drugs and to metabolise many endogenous substances including fatty acids and lysophospholipids. 4. CYP2W1 expression level was suggested to serve as an independent prognostic biomarker in colorectal cancer and hepatocellular carcinoma. The correlation of genetic polymorphisms of CYP2W1 and cancer risk was uncertain. 5. Further characterisation of CYP2W1 structure is suggested to link to its functions. More studies are warranted to reveal the true status and the regulation of CYP2W1 expression across normal and cancer tissues. Catalytic activity of CYP2W1 should be tested on a wider spectrum of endogenous and exogenous substances before its use as the drug target. Larger size of clinical samples can be included to verify the potential of CYP2W1 as the prognostic or cancer risk biomarker.
    Matched MeSH terms: Liver Neoplasms/metabolism; Colorectal Neoplasms/metabolism
  16. Mun KS, Pailoor J, Chan KS, Pillay B
    Malays J Pathol, 2009 Jun;31(1):57-61.
    PMID: 19694315 MyJurnal
    Extra-adrenal paragangliomata are uncommon entities. They can be classified into four basic groups according to their anatomical sites, i.e. branchiomeric, intravagal, aorticosympathetic and visceral autonomic. Similar tumours may arise in sites away from the usual distribution of the sympathetic and parasympathetic ganglia, e.g. orbit, nose, small intestine and even in the pancreas. We report three instructive cases of extra-adrenal paraganglioma which were found in unusual sites such as urinary bladder, thyroid gland and on the wall of the inferior vena cava.
    Matched MeSH terms: Urinary Bladder Neoplasms/metabolism; Thyroid Neoplasms/metabolism; Vascular Neoplasms/metabolism
  17. Stepien M, Duarte-Salles T, Fedirko V, Floegel A, Barupal DK, Rinaldi S, et al.
    Int J Cancer, 2016 Jan 15;138(2):348-60.
    PMID: 26238458 DOI: 10.1002/ijc.29718
    Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
    Matched MeSH terms: Bile Duct Neoplasms/metabolism*; Gallbladder Neoplasms/metabolism*; Liver Neoplasms/metabolism*
  18. Venil CK, Sathishkumar P, Malathi M, Usha R, Jayakumar R, Yusoff ARM, et al.
    Mater Sci Eng C Mater Biol Appl, 2016 Feb;59:228-234.
    PMID: 26652368 DOI: 10.1016/j.msec.2015.10.019
    In this work, the synthesis of silver nanoparticles from a pigment produced by a recently-discovered bacterium, Chryseobacterium artocarpi CECT 8497, was achieved, followed by an investigation of its anticancer properties. The bacterial pigment was identified as flexirubin following NMR ((1)H NMR and (13)C NMR), UV-Vis, and LC-MS analysis. An aqueous silver nitrate solution was treated with isolated flexirubin to produce silver nanoparticles. The synthesised silver nanoparticles were subsequently characterised by UV-Vis spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), X-Ray Diffraction (XRD), and Fourier Transform Infrared (FTIR) Spectroscopy methodologies. Furthermore, the anticancer effects of synthesised silver nanoparticles in a human breast cancer cell line (MCF-7) were evaluated. The tests showed significant cytotoxicity activity of the silver nanoparticles in the cultured cells, with an IC50 value of 36μgmL(-1). This study demonstrates that silver nanoparticles, synthesised from flexirubin from C. artocarpi CECT 8497, may have potential as a novel chemotherapeutic agent.
    Matched MeSH terms: Breast Neoplasms/metabolism
  19. Wong CC, Periasamy N, Sagineedu SR, Sidik S, Sumon SH, Loadman P, et al.
    Invest New Drugs, 2014 Oct;32(5):806-14.
    PMID: 24875131 DOI: 10.1007/s10637-014-0105-6
    Limited tumor penetrability of anti-cancer drugs is recognized as one of the major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2-bromobenzylidene) andrographolide) has been identified as a lead anti-cancer agent for colon cancer. Recently, this compound was shown by us to be a mutant K-Ras binder. In this present study, the penetrability of SRJ09 through the DLD-1 colon cancer multicell layer (MCL) was evaluated. The amount of SRJ09 that penetrated through the MCL was quantitated by utilizing high performance liquid chromatography (HPLC). Histopathological staining was used to visualize the morphology of MCL. A chemosensitivity assay was performed to assess the anti-cancer activity of SRJ09 in DLD-1 cells. SRJ09 was able to penetrate through DLD-1 MCL and is inversely proportional with the MCL thickness. The flow rates for SRJ09 through MCL were 0.90 ± 0.20 μM/min/cm(2) and 0.56 ± 0.06 μM/min/cm(2) for days 1 and 5, respectively, which are better than doxorubicin. Histopathological examination revealed that the integrity of the DLD-1 MCL was retained and no visible damage was inflicted on the cell membrane, confirming the penetration of SRJ09 was by diffusion. Short term exposure (1 h) in DLD-1 cells demonstrated SRJ09 had IC50 of 41 μM which was approximately 4-folds lower than andrographolide, the parent compound of SRJ09. In conclusion, SRJ09 successfully penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to be developed as a clinically viable anti-colon cancer drug.
    Matched MeSH terms: Colonic Neoplasms/metabolism*
  20. Pandurangan AK, Esa NM
    Asian Pac J Cancer Prev, 2013;14(10):5543-52.
    PMID: 24289544
    Colorectal cancer (CRC), a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation, and programmed cell death, is the third most common malignant neoplasm worldwide. A number of promising targets such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related factor 2 (Nrf2), Wnt/β-catenin, Notch and apoptotic signaling have been identified by researchers as useful targets to prevent or therapeutically inhibit colon cancer development. In this review article, we aimed to explore the current targets available to eliminate colon cancer with an update of dietary and non-nutritional compounds that could be of potential use for interaction with regulatory molecules to prevent CRC.
    Matched MeSH terms: Colorectal Neoplasms/metabolism*
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