Displaying publications 1 - 20 of 46 in total

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  1. Dietary non-nutritive factors in targeting of regulatory molecules in colorectal cancer: an update
    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*
  2. Green fabrication of biologically active magnetic core-shell Fe3O4/Au nanoparticles and their potential anticancer effect
    Izadiyan Z, Shameli K, Miyake M, Teow SY, Peh SC, Mohamad SE, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 Mar;96:51-57.
    PMID: 30606561 DOI: 10.1016/j.msec.2018.11.008
    Core-shell Fe3O4/Au nanostructures were constructed using an advanced method of two-step synthesis from Juglans regia (walnut) green husk extract. Several complementary methods were applied to investigate structural and magnetic properties of the samples. X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), electron diffraction, optical, thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM) were used for nanoparticle characterizations. As shown by HR-TEM, the mean diameter of core-shell Fe3O4/Au nanoparticles synthesized using co-precipitation method was 6.08 ± 1.06 nm. This study shows that the physical and structural properties of core-shell Fe3O4/Au nanoparticles possess intrinsic properties of gold and magnetite. VSM revealed that the core-shell Fe3O4/Au have high saturation magnetization and low coercivity due to the magnetic properties. The core-shell nanoparticles show the inhibitory concentration (IC)50 of 235 μg/ml against a colorectal cancer cell line, HT-29. When tested against non-cancer cells, IC50 was not achieved even up to 500 μg/ml. This study highlights the magnetic properties and anticancer action of core-shell Fe3O4/Au nanoparticles. This compound can be ideal candidate for cancer treatment and other biomedical applications.
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  3. A novel role for estrogen-induced signaling in the colorectal cancer gender bias
    Haziman AA, Ravinderan S, Thangavelu T, Thomas W
    Ir J Med Sci, 2019 May;188(2):389-395.
    PMID: 30014247 DOI: 10.1007/s11845-018-1867-1
    Colorectal cancer (CRC) is a malignancy whose incidence is increasing globally, and there is a gender difference in the increasing risk. Evidence from hormone replacement therapy studies points to a role for circulating estrogens in suppressing the development of CRC. Estrogen receptor-β has been identified as a tumor suppressor, but other actions of estrogen may also contribute to the difference in CRC incidence between men and women. The KCNQ1/KCNE3 potassium channel is regulated by estrogen in order to modulate chloride secretion during the menstrual cycle; the effect of estrogen on the colon is to promote fluid conservation during the implantation window. KCNQ1 is also a tumor suppressor in CRC, and its sustained expression has been linked to suppression of the Wnt/β-catenin signaling pathway that contributes to CRC tumor progression. KCNQ1 regulation may represent a link between the normal physiological actions of estrogen in the colon and the hormone's apparent tumor-suppressive effects in CRC development.
    Matched MeSH terms: Colorectal Neoplasms/metabolism*
  4. PIK3CA gene mutations in breast carcinoma in Malaysian patients
    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: Colorectal Neoplasms/metabolism
  5. Predictive Potential of PD-L1, TYMS, and DCC Expressions in Treatment Outcome of Colorectal Carcinoma
    Onwe EE, Ghani FA, Abdullah M, Osman M, Zin RRM, Vivian AN, et al.
    Adv Exp Med Biol, 2020;1292:97-112.
    PMID: 32542457 DOI: 10.1007/5584_2020_521
    Colorectal carcinoma (CRC) is a malignancy of epithelial origin in the large bowel. The elucidation of the biological functions of programmed cell death ligand-1 (PD-L1), thymidylate synthase (TYMS), and deleted in colorectal cancer (DCC) biomarkers including their roles in the pathophysiology of CRC - has led to their applications in diagnostic and chemo-pharmaceutics. We investigated whether PD-L1, TYMS, and DCC protein expression in CRC tumors are predictive biomarkers of treatment outcome for CRC patients. The expressions of PD-L1, TYMS, and DCC were evaluated by immunohistochemistry (IHC) in 91 paraffin-embedded samples from patients who underwent colectomy procedure in Hospital Serdang, Selangor, Malaysia. There was high expression of DCC in most cases: 84.6% (77/91). PD-L1 showed low expression in 93.4% (86/91) of cases and high expression in 6.6% (5/91) of cases. Low and high expressions of TYMS were detected in 53.8% (49/91) and 46.2% (42/91) of the CRC cases, respectively. There was a significant association between the TYMS expression and gender (P 
    Matched MeSH terms: Colorectal Neoplasms/metabolism*
  6. Fulltext Loss of Interleukin-17RA Expression is Associated with Tumour Progression in Colorectal Carcinoma
    Chai BY, Yip WK, Dusa N, Mohtarrudin N, Seow HF
    Pathol Oncol Res, 2020 Oct;26(4):2291-2298.
    PMID: 32462420 DOI: 10.1007/s12253-020-00820-4
    Interleukin-17 (IL-17) is a pro-inflammatory cytokine found in various cancers. Current evidence indicates that IL-17 plays a vital role in tumour initiation and progression in colorectal carcinoma (CRC) via binding with its receptor, IL-17RA. However, the association between clinicopathological features and presence of IL-17 and IL-17RA protein in primary CRC tissues remains unclear. This study also investigates the difference between the presence of IL-17 and IL-17RA in the paired tumour tissues versus adjacent normal tissues. The presence of IL-17RA and IL-17 protein in primary CRC tissues was determined by immunohistochemistry. Associations between clinicopathological features and IL-17RA and IL-17 immunoreactivity, were analyzed by χ2 tests. We found that both IL-17RA (p = 0.001) and IL-17 (p = 0.025) in tumour cells of primary CRC tissues was significantly lower as compared to adjacent normal tissue. Positive immunoreactivity for IL-17RA and IL-17 were detected in 51.0% and 16.8% of tumour tissues, respectively. Furthermore, negative immunoreactivity of IL-17R was significantly associated with advanced stage according to TNM classifier (p = 0.027), high grade of tumour (p = 0.019), increased depth of tumour invasion (p = 0.023) and vascular invasion (p = 0.039). Positive IL-17 immunoreactivity was associated with advanced stage (p = 0.008) and lymph node metastasis (p = 0.008). Thus, this study suggests that the loss of IL-17RA expression occurs as tumour progresses and this may predict the aggressiveness of tumour whilst expression of IL-17 promotes tumour progression and lymph node metastasis. Thus, loss of IL-17RA could be a useful prognostic biomarker for tumour progression in CRC patients.
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  7. Histone Deacetylase Inhibitors for the Treatment of Colorectal Cancer: Recent Progress and Future Prospects
    Singh A, Patel P, Patel VK, Jain DK, Veerasamy R, Sharma PC, et al.
    Curr Cancer Drug Targets, 2017;17(5):456-466.
    PMID: 28067178 DOI: 10.2174/1568009617666170109150134
    BACKGROUND: Colorectal cancer is a devastating disease with a dismal prognosis which is heavily hampered by delayed diagnosis. Surgical resection, radiation therapy and chemotherapy are the curative options. Due to few therapeutic treatments available i.e., mono and combination therapy and development of resistance towards drug response, novel and efficacious therapy are urgently needed.

    OBJECTIVE: In this study, we have studied the potential of histone deacetylase inhibitors in colorectal cancer.

    RESULTS: Histone deacetylase inhibitors (HDACIs) are an emerging class of therapeutic agents having potential anticancer activity with minimal toxicity for different types of malignancies in preclinical studies. HDACIs have proven less effective in monotherapy thus the combination of HDACIs with other anticancer agents are being assessed for the treatment of colorectal cancer.

    CONCLUSION: The molecular mechanism emphasizing the anticancer effect of HDACIs in colorectal cancer was illustrated and a recapitulation was carried out on the recent advances in the rationale behind combination therapies currently underway in clinical evaluations.

    Matched MeSH terms: Colorectal Neoplasms/metabolism
  8. Probing the colorectal cancer proteome for biomarkers: Current status and perspectives
    Lee PY, Chin SF, Low TY, Jamal R
    J Proteomics, 2018 09 15;187:93-105.
    PMID: 29953962 DOI: 10.1016/j.jprot.2018.06.014
    Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Biomarkers that can facilitate better clinical management of CRC are in high demand to improve patient outcome and to reduce mortality. In this regard, proteomic analysis holds a promising prospect in the hunt of novel biomarkers for CRC and in understanding the mechanisms underlying tumorigenesis. This review aims to provide an overview of the current progress of proteomic research, focusing on discovery and validation of diagnostic biomarkers for CRC. We will summarize the contributions of proteomic strategies to recent discoveries of protein biomarkers for CRC and also briefly discuss the potential and challenges of different proteomic approaches in biomarker discovery and translational applications.
    Matched MeSH terms: Colorectal Neoplasms/metabolism*
  9. HMGB1: an overview of its versatile roles in the pathogenesis of colorectal cancer
    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: Colorectal Neoplasms/metabolism
  10. Fulltext An Association Map on the Effect of Flavonoids on the Signaling Pathways in Colorectal Cancer
    Koosha S, Alshawsh MA, Looi CY, Seyedan A, Mohamed Z
    Int J Med Sci, 2016;13(5):374-85.
    PMID: 27226778 DOI: 10.7150/ijms.14485
    Colorectal cancer (CRC) is the third most common type of cancer in the world, causing thousands of deaths annually. Although chemotherapy is known to be an effective treatment to combat colon cancer, it produces severe side effects. Natural products, on the other hand, appear to generate fewer side effects than do chemotherapeutic drugs. Flavonoids are polyphenolic compounds found in various fruits and vegetables known to possess antioxidant activities, and the literature shows that several of these flavonoids have anti-CRC propertiesFlavonoids are classified into five main subclasses: flavonols, flavanones, flavones, flavan-3-ols, and flavanonols. Of these subclasses, the flavanonols have a minimum effect against CRC, whereas the flavones play an important role. The main targets for the inhibitory effect of flavonoids on CRC signaling pathways are caspase; nuclear factor kappa B; mitogen-activated protein kinase/p38; matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9; p53; β-catenin; cyclin-dependent kinase (CDK)2 and CDK4; and cyclins A, B, D, and E. In this review article, we summarize the in vitro and in vivo studies that have been performed since 2000 on the anti-CRC properties of flavonoids. We also describe the signaling pathways affected by flavonoids that have been found to be involved in CRC. Some flavonoids have the potential to be an effective alternative to chemotherapeutic drugs in the treatment of colon cancer; well-controlled clinical studies should, however, be conducted to support this proposal.
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  11. Cytochrome P450 2W1 (CYP2W1) - ready for use as the biomarker and drug target for cancer?
    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: Colorectal Neoplasms/metabolism
  12. Fulltext CD133 marks for colorectal adenocarcinoma
    Chew MF, Teoh KH, Cheah PL
    Malays J Pathol, 2012 Jun;34(1):25-8.
    PMID: 22870594 MyJurnal
    CD133, a marker which has been advocated to mark colorectal carcinoma "stem or tumour initiating cells" is amongst the frequently studied markers in colorectal cancer. A study was conducted at the Department of Pathology, University of Malaya Medical Centre to determine the expression of CD133 in 56 archived, formalin-fixed, paraffin-embedded colorectal adenocarcinoma in comparison with adjacent benign colorectal epithelium by immunohistochemical staining for CD133 expression. CD133 immunopositivity was determined as staining at the glandular luminal surface or in the intraluminal debris. Expression was semiquantitated for (1) proportion of CD133 immunopositivity in the malignant or adjacent benign colorectal epithelium and (2) intensity of staining. The final score of CD133 immunopositivity was arbitrarily taken as proportion of CD133 immunopositivity multiplied by intensity of staining in both the malignant and adjacent benign colorectal epithelium. CD133 expression was observed in significantly increased frequency in 49 (87.5%) colorectal adenocarcinoma compared with 15 (26.8%) of the adjacent benign colorectal epithelium (p<0.05). In terms of immunopositivity score (proportion of CD133 immunopositivity multiplied by intensity of staining), colorectal adenocarcinoma had a mean arbitrary score of 8.5 which was significantly higher than the mean immunopositivity score of 0.5 of the adjacent benign colorectal epithelium (p<0.05). In addition, the maximum immunopositivity score for the adjacent benign colorectal epithelium was 4, while 38 (67.9%) of colorectal adenocarcinoma had scores >4. This study shows that CD133 is able to mark colorectal adenocarcinoma but it is still unclear at this juncture whether CD133 is indeed a marker for colorectal adenocarcinoma "stem cells".
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  13. Analysis of differentially expressed proteins in colorectal cancer using hydroxyapatite column and SDS-PAGE
    Lim SR, Gooi BH, Singh M, Gam LH
    Appl Biochem Biotechnol, 2011 Nov;165(5-6):1211-24.
    PMID: 21863284 DOI: 10.1007/s12010-011-9339-3
    Limitation on two dimensional (2D) gel electrophoresis technique causes some proteins to be under presented, especially the extreme acidic, basic, or membrane proteins. To overcome the limitation of 2D electrophoresis, an analysis method was developed for identification of differentially expressed proteins in normal and cancerous colonic tissues using self-pack hydroxyapatite (HA) column. Normal and cancerous colon tissues were homogenized and proteins were extracted using sodium phosphate buffer at pH 6.8. Protein concentration was determined and the proteins were loaded unto the HA column. HA column reduced the complexity of proteins mixture by fractionating the proteins according to their ionic strength. Further protein separation was accomplished by a simple and cost effective sodium dodecyl sulfate-polyacrylamide gel electrophoresis method. The protein bands were subjected to in-gel digestion and protein analysis was performed using electrospray ionization (ESI) ion trap mass spectrometer. There were 17 upregulated proteins and seven downregulated proteins detected with significant differential expression. Some of these proteins were low abundant proteins or proteins with extreme pH that were usually under presented in 2D gel analysis. We have identified brain mitochondrial carrier protein 1, T-cell surface glycoprotein CD1a, SOSS complex subunit B2, and Protein Jade 1 which were previously not detected in 2D gel analysis method.
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  14. Identification of low abundance proteins in colorectal cancer tissues
    Lim SR, Gooi BH, Gam LH
    Cancer Biomark, 2012;12(4):185-98.
    PMID: 23568009 DOI: 10.3233/CBM-130307
    Detection of low abundance proteins always possesses challenges even with the currently available proteomics technologies.
    Matched MeSH terms: Colorectal Neoplasms/metabolism*
  15. Fulltext Water extract of brewers' rice induces apoptosis in human colorectal cancer cells via activation of caspase-3 and caspase-8 and downregulates the Wnt/β-catenin downstream signaling pathway in brewers' rice-treated rats with azoxymethane-induced colon carcinogenesis
    Tan BL, Norhaizan ME, Huynh K, Heshu SR, Yeap SK, Hazilawati H, et al.
    BMC Complement Altern Med, 2015;15:205.
    PMID: 26122204 DOI: 10.1186/s12906-015-0730-4
    Brewers' rice, is locally known as temukut, is a mixture of broken rice, rice bran, and rice germ. The current study is an extension of our previous work, which demonstrated that water extract of brewers' rice (WBR) induced apoptosis in human colorectal cancer (HT-29) cells. We also identified that brewers' rice was effective in reducing the tumor incidence and multiplicity in azoxymethane (AOM)-injected colon cancer rats. Our present study was designed to identify whether WBR confers an inhibitory effect via the regulation of upstream components in the Wnt signaling pathway in HT-29 cells. To further determine whether the in vitro mechanisms of action observed in the HT-29 cells inhibit the downstream signaling target of the Wnt/β-catenin pathway, we evaluated the mechanistic action of brewers' rice in regulating the expressions and key protein markers during colon carcinogenesis in male Sprague-Dawley rats.
    Matched MeSH terms: Colorectal Neoplasms/metabolism*
  16. Fulltext Overexpression of WNT2 and TSG101 genes in colorectal carcinoma
    Ma XR, Edmund Sim UH, Pauline B, Patricia L, Rahman J
    Trop Biomed, 2008 Apr;25(1):46-57.
    PMID: 18600204 MyJurnal
    Colorectal carcinoma (CRC) arises as a result of mutational activation of oncogenes coupled with inactivation of tumour suppressor genes. Mutations in APC, K-ras and p53 have been commonly reported. In a previous study by our group, the tumour susceptibility gene 101 (TSG101) were found to be persistently upregulated in CRC cases. TSG101 was reported to be closely related to cancers of the breast, brain and colon, and its overexpression in human papillary thyroid carcinomas and ovarian carcinomas had previously been reported. The wingless-type MMTV integration site family member 2 (WNT2) is potentially important in the Wnt/beta-catenin pathway and upregulation of WNT2 is not uncommon in human cancers. In this study, we report the investigation for mutation(s) and expression pattern(s) of WNT2 and TSG101, in an effort to further understand their role(s) in CRC tumourigenesis. Our results revealed no mutation in these genes, despite their persistent upregulation in CRC cases studied.
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  17. Anticancer activities of a benzimidazole compound through sirtuin inhibition in colorectal cancer
    Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

    Matched MeSH terms: Colorectal Neoplasms/metabolism
  18. Fulltext In-Vitro and In-Silico Evaluations of Heterocyclic-Containing Diarylpentanoids as Bcl-2 Inhibitors Against LoVo Colorectal Cancer Cells
    Leong SW, Chia SL, Abas F, Yusoff K
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858795 DOI: 10.3390/molecules25173877
    In the present study, we investigated the in-vitro anti-cancer potential of six diarylpentanoids against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, SW620, LoVo, HT29, NCI-H508, RKO, and LS411N cells. Structure-activity relationship study suggested that the insertions of tetrahydro-4H-thiopyran-4-one and brominated phenyl moieties are essential for better cytotoxicity. Among the evaluated analogs, 2e has been identified as the lead compound due to its low IC50 values of approximately 1 µM across all cancer cell lines and high chemotherapeutic index of 7.1. Anti-proliferative studies on LoVo cells showed that 2e could inhibit cell proliferation and colony formations by inducing G2/M cell cycle arrest. Subsequent cell apoptosis assay confirmed that 2e is a Bcl-2 inhibitor that could induce intrinsic cell apoptosis by creating a cellular redox imbalance through its direct inhibition on the Bcl-2 protein. Further molecular docking studies revealed that the bromophenyl moieties of 2e could interact with the Bcl-2 surface pocket through hydrophobic interaction, while the tetrahydro-4H-thiopyran-4-one fragment could form additional Pi-sulfur and Pi-alkyl interactions in the same binding site. In all, the present results suggest that 2e could be a potent lead that deserves further modification and investigation in the development of a new Bcl-2 inhibitor.
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  19. Luteolin, a bioflavonoid inhibits colorectal cancer through modulation of multiple signaling pathways: a review
    Pandurangan AK, Esa NM
    Asian Pac J Cancer Prev, 2014;15(14):5501-8.
    PMID: 25081655
    Luteolin, 3', 4', 5,7-tetrahydroxyflavone, belongs to a group of naturally occurring compounds called flavonoids that are found widely in the plant kingdom. It possesses many beneficial properties including antioxidant, anti- inflammatory, anti-bacterial, anti-diabetic and anti-proliferative actions. Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Many signaling pathways are deregulated during the progression of colon cancer. In this review we aimed to analyze the protection offered by luteolin on colon cancer. During colon cancer genesis, luteolin known to reduce oxidative stress thereby protects the cell to undergo damage in vivo. Wnt/β-catenin signaling, deregulated during neoplastic development, is modified by luteolin. Hence, luteolin can be considered as a potential drug to treat CRC.
    Matched MeSH terms: Colorectal Neoplasms/metabolism
  20. Fulltext The involvement of miR-23a/APAF1 regulation axis in colorectal cancer
    Yong FL, Wang CW, Roslani AC, Law CW
    Int J Mol Sci, 2014 Jul 02;15(7):11713-29.
    PMID: 24992592 DOI: 10.3390/ijms150711713
    Recent advances in microRNAome have made microRNAs (miRNAs) a compelling novel class of biomarker in cancer biology. In the present study, the role of miR-23a in the carcinogenesis of colorectal cancer (CRC) was investigated. Cell viability, apoptosis, and caspase 3/7 activation analyses were conducted to determine the potentiality of apoptosis resistance function of miR-23a in CRC. Luciferase assay was performed to verify a putative target site of miR-23a in the 3'-UTR of apoptosis protease activating factor 1 (APAF1) mRNA. The expression levels of miR-23a and APAF1 in CRC cell lines (SW480 and SW620) and clinical samples were assessed using reverse transcription-quantitative real-time PCR (RT-qPCR) and Western blot. We found that the inhibition of miR-23a in SW480 and SW620 cell lines resulted in significant reduction of cell viability and promotion of cell apoptosis. Moreover, miR-23a up-regulation was coupled with APAF1 down-regulation in CRC tissue samples. Taken together, miR-23a was identified to regulate apoptosis in CRC. Our study highlights the potential application of miR-23a/APAF1 regulation axis in miRNA-based therapy and prognostication.
    Matched MeSH terms: Colorectal Neoplasms/metabolism*
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