Displaying publications 21 - 40 of 69 in total

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  1. Damnacanthal: a promising compound as a medicinal anthraquinone
    Abu N, Ali NM, Ho WY, Yeap SK, Aziz MY, Alitheen NB
    Anticancer Agents Med Chem, 2014 Jun;14(5):750-5.
    PMID: 24164045
    The Noni fruit, or scientifically known as Morinda citrifolia can be found in various parts of the world, especially in the pacific region. It is a small evergreen bushy-like tree originated from the Rubiaceae family. The plant has been used by polynesians as a medicinal herb for more than 2000 years. A substantial amount of phytochemicals can be found in the roots of this plant. Among all, damnacanthal has been found to be the most interesting, versatile and potent compound. Damnacanthal or chemically known as,3- hydroxy-1-methoxyanthraquinone-2-caboxaldehyde (C16H10O5), appears as pale yellow crystals with a melting point of 210-211 °C. This compound is of particular interest due to its striking pharmacological properties. Damnacanthal was shown to inhibit the oncogene Ras, p56lck tyrosine kinase, NF-KB pathway and induce apoptosis in vitro. This review aims to discuss the biological properties of damnacanthal, specifically on its anti-cancer activity that has been reported.
  2. Signatures of gene expression, DNA methylation and microRNAs of hepatocellular carcinoma with vascular invasion
    Sulaiman SA, Abu N, Ab-Mutalib NS, Low TY, Jamal R
    Future Oncol, 2019 Aug;15(22):2603-2617.
    PMID: 31339048 DOI: 10.2217/fon-2018-0909
    Aim: Micro and macro vascular invasion (VI) are known as independent predictors of tumor recurrence and poor survival after surgical treatment of hepatocellular carcinoma (HCC). Here, we aimed to re-analyze The Cancer Genome Atlas of liver hepatocellular carcinoma datasets to identify the VI-expression signatures. Materials & methods: We filtered The Cancer Genome Atlas liver hepatocellular carcinoma (LIHC) datasets into three groups: no VI (NVI = 198); micro VI (MIVI = 89) and macro VI (MAVI = 16). We performed differential gene expression, methylation and microRNA analyses. Results & conclusion: We identified 12 differentially expressed genes and 55 differentially methylated genes in MAVI compared with no VI. The GPD1L gene appeared in all of the comparative analyses. Higher GPD1L expression was associated with VI and poor outcomes in the HCC patients.
  3. Prospective Advances in Circular RNA Investigation
    Sulaiman SA, Abdul Murad NA, Mohamad Hanif EA, Abu N, Jamal R
    Adv Exp Med Biol, 2018 9 28;1087:357-370.
    PMID: 30259380 DOI: 10.1007/978-981-13-1426-1_28
    circRNAs have emerged as one of the key regulators in many cellular mechanisms and pathogenesis of diseases. However, with the limited knowledge and current technologies for circRNA investigations, there are several challenges that need to be addressed for. These include challenges in understanding the regulation of circRNA biogenesis, experimental designs, and sample preparations to characterize the circRNAs in diseases as well as the bioinformatics pipelines and algorithms. In this chapter, we discussed the above challenges and possible strategies to overcome those limitations. We also addressed the differences between the existing applications and technologies to study the circRNAs in diseases. By addressing these challenges, further understanding of circRNAs roles and regulations as well as the discovery of novel circRNAs could be achieved.
  4. Fulltext Circular RNAs: Potential Regulators of Treatment Resistance in Human Cancers
    Jeyaraman S, Hanif EAM, Ab Mutalib NS, Jamal R, Abu N
    Front Genet, 2019;10:1369.
    PMID: 32047511 DOI: 10.3389/fgene.2019.01369
    Circular RNAs (circRNAs) which were once considered as "junk" are now in the spotlight as a potential player in regulating human diseases, especially cancer. With the development of high throughput technologies in recent years, the full potential of circRNAs is being uncovered. CircRNAs possess some unique characteristics and advantageous properties that could benefit medical research and clinical applications. CircRNAs are stable with covalently closed loops that are resistant to ribonucleases, have disease stage-specific expressions and are selectively abundant in different types of tissues. Interestingly, the presence of circRNAs in different types of treatment resistance in human cancers was recently observed with the involvement of a few key pathways. The activation of certain pathways by circRNAs may give new insights to treatment resistance management. The potential usage of circRNAs from this aspect is very much in its infancy stage and has not been fully validated. This mini-review attempts to highlight the possible role of circRNAs as regulators of treatment resistance in human cancers based on its intersection molecules and cancer-related regulatory networks.
  5. HER2/neu-Based Peptide Vaccination-Pulsed with B-Cell Epitope Induced Efficient Prophylactic and Therapeutic Antitumor Activities in TUBO Breast Cancer Mice Model
    Nordin ML, Mohamad Norpi AS, Ng PY, Yusoff K, Abu N, Lim KP, et al.
    Cancers (Basel), 2021 Oct 01;13(19).
    PMID: 34638441 DOI: 10.3390/cancers13194958
    Breast cancer is the most common invasive cancer diagnosed among women. A cancer vaccine has been recognized as a form of immunotherapy with a prominent position in the prevention and treatment of breast cancer. The majority of current breast cancer vaccination strategies aim to stimulate antitumor T-cell responses of the HER2/neu oncogene, which is abnormally expressed in breast cancer cells. However, the role of the B-cell humoral response is often underappreciated in the cancer vaccine design. We have advanced this idea by elucidating the role of B-cells in cancer vaccination by designing a chimeric antigenic peptide possessing both cytotoxic T lymphocytes (GP2) and B-cell (P4) peptide epitopes derived from HER2/neu. The chimeric peptide (GP2-P4) was further conjugated to a carrier protein (KLH), forming a KLH-GP2-P4 conjugate. The immunogenicity of KLH-GP2-P4 was compared with KLH-GP2 (lacking the B-cell epitope) in BALB/c mice. Mice immunized with KLH-GP2-P4 elicited more potent antigen-specific neutralizing antibodies against syngeneic TUBO cells (cancer cell line overexpressing HER2/neu) that was governed by a balanced Th1/Th2 polarization in comparison to KLH-GP2. Subsequently, these immune responses led to greater inhibition of tumor growth and longer survival in TUBO tumor-bearing mice in both prophylactic and therapeutic challenge experiments. Overall, our data demonstrated that the B-cell epitope has a profound effect in orchestrating an efficacious antitumor immunity. Thus, a multi-epitope peptide vaccine encompassing cytotoxic T-lymphocytes, T-helper and B-cell epitopes represents a promising strategy in developing cancer vaccines with a preventive and therapeutic modality for the effective management of breast cancer.
  6. LOC285629 regulates cell proliferation and motility in colorectal cancer cells
    Nasir SN, Abu N, Ab Mutalib NS, Ishak M, Sagap I, Mazlan L, et al.
    Clin Transl Oncol, 2018 Jun;20(6):775-784.
    PMID: 29098557 DOI: 10.1007/s12094-017-1788-x
    PURPOSE: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.

    METHOD: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.

    RESULTS: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.

    CONCLUSION: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

  7. Fulltext Gene Expression Analysis Reveals the Concurrent Activation of Proapoptotic and Antioxidant-Defensive Mechanisms in Flavokawain B-Treated Cervical Cancer HeLa Cells
    Yeap SK, Abu N, Akthar N, Ho WY, Ky H, Tan SW, et al.
    Integr Cancer Ther, 2017 09;16(3):373-384.
    PMID: 27458249 DOI: 10.1177/1534735416660383
    Flavokawain B (FKB) is known to possess promising anticancer abilities. This is demonstrated in various cancer cell lines including HeLa cells. Cervical cancer is among the most widely diagnosed cancer among women today. Though FKB has been shown to be effective in treating cancer cells, the exact molecular mechanism is still unknown. This study is aimed at understanding the effects of FKB on HeLa cells using a microarray-based mRNA expression profiling and proteome profiling of stress-related proteins. The results of this study suggest that FKB induced cell death through p21-mediated cell cycle arrest and activation of p38. However, concurrent activation of antioxidant-related pathways and iron sequestration pathway followed by activation of ER-resident stress proteins clearly indicate that FKB failed to induce apoptosis in HeLa cells via oxidative stress. This effect implies that the protection of HeLa cells by FKB from H2O2-induced cell death is via neutralization of reactive oxygen species.
  8. Fulltext A Unique Case of Unilateral Oculomotor Nerve Palsy Secondary to Dengue Fever
    Loh SA, Wan Abdul Rahman WMH, Sonny Teo KS, Abu N
    Cureus, 2023 Feb;15(2):e35281.
    PMID: 36994298 DOI: 10.7759/cureus.35281
    A wide range of ocular complications may arise from the mosquito-borne illness, dengue fever. We report a case of isolated unilateral oculomotor nerve palsy due to complications of dengue fever. A 50-year-old male with serologically confirmed dengue fever presented with a sudden onset of double vision with left eyelid drooping and left eye outward deviation on his day 8 of illness. Ocular examination revealed binocular diplopia with complete left eye ptosis and restriction of all left eye movements except for abduction. His left eye pupil was 8 mm dilated with a negative relative afferent pupillary defect (RAPD). A clinical diagnosis of left eye oculomotor nerve palsy with pupil involvement was established. Urgent contrasted brain imaging tests were performed and revealed to be normal. He was managed conservatively and had complete resolution of symptoms with good vision recovery within 3.5 months. Cranial mononeuropathy may be one of the various complications following dengue fever, as demonstrated in this case report. As it is an uncommon presentation, there is a need to exclude other acute causes of cranial nerve palsy. Visual prognosis is still favorable with judicious monitoring and without any treatment of steroids or immunoglobulin.
  9. Fulltext Methylation Profile of Cancer Testis Antigens in Colorectal Cancer
    Abu N, Rus Bakarurraini NAA, Nasir SN, Ishak M, Baharuddin R, Jamal R, et al.
    Iran J Immunol, 2023 Mar 14;20(1):83-91.
    PMID: 36932973 DOI: 10.22034/iji.2023.92600.2171
    BACKGROUND: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.

    OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.

    METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.

    RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.

    CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.

  10. Fulltext Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer
    Hon KW, Ab-Mutalib NS, Abdullah NMA, Jamal R, Abu N
    Sci Rep, 2019 Nov 11;9(1):16497.
    PMID: 31712601 DOI: 10.1038/s41598-019-53063-y
    Chemo-resistance is associated with poor prognosis in colorectal cancer (CRC), with the absence of early biomarker. Exosomes are microvesicles released by body cells for intercellular communication. Circular RNAs (circRNAs) are non-coding RNAs with covalently closed loops and enriched in exosomes. Crosstalk between circRNAs in exosomes and chemo-resistance in CRC remains unknown. This research aims to identify exosomal circRNAs associated with FOLFOX-resistance in CRC. FOLFOX-resistant HCT116 CRC cells (HCT116-R) were generated from parental HCT116 cells (HCT116-P) using periodic drug induction. Exosomes were characterized using transmission electron microscopy (TEM), Zetasizer and Western blot. Our exosomes were translucent cup-shaped structures under TEM with differential expression of TSG101, CD9, and CD63. We performed circRNAs microarray using exosomal RNAs from HCT116-R and HCT116-P cells. We validated our microarray data using serum samples. We performed drug sensitivity assay and cell cycle analysis to characterize selected circRNA after siRNA-knockdown. Using fold change >2 and p 
  11. Fulltext The flavokawains: uprising medicinal chalcones
    Abu N, Ho WY, Yeap SK, Akhtar MN, Abdullah MP, Omar AR, et al.
    Cancer Cell Int, 2013 Oct 22;13(1):102.
    PMID: 24148263 DOI: 10.1186/1475-2867-13-102
    Plant-based compounds have been in the spotlight in search of new and promising drugs. Flavokawain A, B and C are naturally occurring chalcones that have been isolated from several medicinal plants; namely the piper methysticum or commercially known as the kava-kava. Multiple researches have been done to evaluate the bioactivities of these compounds. It has been shown that all three flavokawains may hold promising anti-cancer effects. It has also been revealed that both flavokawain A and B are involved in the induction of cell cycle arrest in several cancer cell lines. Nevertheless, flavokawain B was shown to be more effective in treating in vitro cancer cell lines as compared to flavokawain A and C. Flavokawain B also exerts antinociceptive effects as well as anti-inflammation properties. This mini-review attempts to discuss the biological properties of all the flavokawains that have been reported.
  12. Fulltext Single Cell Transcriptome in Colorectal Cancer-Current Updates on Its Application in Metastasis, Chemoresistance and the Roles of Circulating Tumor Cells
    Tieng FYF, Baharudin R, Abu N, Mohd Yunos RI, Lee LH, Ab Mutalib NS
    Front Pharmacol, 2020;11:135.
    PMID: 32174835 DOI: 10.3389/fphar.2020.00135
    Colorectal cancer (CRC) is among the most common cancer worldwide, a challenge for research, and a model for studying the molecular mechanisms involved in its development. Previously, bulk transcriptomics analyses were utilized to classify CRC based on its distinct molecular and clinicopathological features for prognosis and diagnosis of patients. The introduction of single-cell transcriptomics completely turned the table by enabling the examination of the expression levels of individual cancer cell within a single tumor. In this review, we highlighted the importance of these single-cell transcriptomics analyses as well as suggesting circulating tumor cells (CTCs) as the main focus of single-cell RNA sequencing. Characterization of these cells might reveal the intratumoral heterogeneity present in CRC while providing critical insights into cancer metastasis. To summarize, we believed the analysis of gene expression patterns of CTC from CRC at single-cell resolution holds the potential to provide key information for identification of prognostic and diagnostic markers as well as the development of precise and personalized cancer treatment.
  13. Fulltext Characterisation of sol-gel method synthesised MgZnFe2O4 nanoparticles and its cytotoxic effects on breast cancer cell line, MDA MB-231 in vitro
    Nordin N, Kanagesan S, Zamberi NR, Yeap SK, Abu N, Tamilselvan S, et al.
    IET Nanobiotechnol, 2017 Apr;11(3):343-348.
    PMID: 28476993 DOI: 10.1049/iet-nbt.2016.0007
    In this study, nanocrystalline magnesium zinc ferrite nanoparticles were successfully prepared by a simple sol-gel method using copper nitrate and ferric nitrate as raw materials. The calcined samples were characterised by differential thermal analysis/thermogravimetric analysis, Fourier transform infrared spectroscopy and X-ray diffraction. Transmission electron microscopy revealed that the average particle size of the calcined sample was in a range of 17-41 nm with an average of 29 nm and has spherical size. A cytotoxicity test was performed on human breast cancer cells (MDA MB-231) and (MCF-7) at various concentrations starting from (0 µg/ml) to (800 µg/ml). The sample possessed a mild toxic effect toward MDA MB-231 and MCF-7 after being examined with MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay for up to 72 h of incubation. Higher reduction of cells viability was observed as the concentration of sample was increased in MDA MB-231 cell line than in MCF-7. Therefore, further cytotoxicity tests were performed on MDA MB-231 cell line.
  14. Fulltext Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy
    Bwatanglang IB, Mohammad F, Yusof NA, Abdullah J, Hussein MZ, Alitheen NB, et al.
    Int J Nanomedicine, 2016;11:413-28.
    PMID: 26858524 DOI: 10.2147/IJN.S90198
    In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange-red fluorescence around 600 nm and investigated to the highest intensity at Mn(2+) doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging.
  15. Fulltext 3-Bromo-1-hydroxy-9,10-anthraquinone (BHAQ) inhibits growth and migration of the human breast cancer cell lines MCF-7 and MDA-MB231
    Abu N, Akhtar MN, Ho WY, Yeap SK, Alitheen NB
    Molecules, 2013 Aug 27;18(9):10367-77.
    PMID: 23985955 DOI: 10.3390/molecules180910367
    Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 and MDA-MB231. Anthraquinones are an interesting class of molecules that display a wide spectrum of biological applications, including anticancer properties. Cellular inhibition was tested through a MTT assay, double acridine orange/propidium iodide staining and FACS cell cycle analysis. Inhibition of migration was tested by the wound healing method, and migration through a Boyden chamber. BHAQ was cytotoxic towards both cell lines in a dose dependent and possibly cell-dependent manner. Additionally, BHAQ also inhibited the migration of the highly metastatic MDA-MB231 cell line.
  16. Fulltext Dual Regulation of Cell Death and Cell Survival upon Induction of Cellular Stress by Isopimara-7,15-Dien-19-Oic Acid in Cervical Cancer, HeLa Cells In vitro
    Abu N, Yeap SK, Pauzi AZ, Akhtar MN, Zamberi NR, Ismail J, et al.
    Front Pharmacol, 2016;7:89.
    PMID: 27065873 DOI: 10.3389/fphar.2016.00089
    The Fritillaria imperialis is an ornamental flower that can be found in various parts of the world including Iraq, Afghanistan, Pakistan, and the Himalayas. The use of this plant as traditional remedy is widely known. This study aims to unveil the anti-cancer potentials of Isopimara-7,15-Dien-19-Oic Acid, extracted from the bulbs of F. imperialis in cervical cancer cell line, HeLa cells. Flow cytometry analysis of cell death, gene expression analysis via cDNA microarray and protein array were performed. Based on the results, Isopimara-7,15-Dien-19-Oic acid simultaneously induced cell death and promoted cell survival. The execution of apoptosis was apparent based on the flow cytometry results and regulation of both pro and anti-apoptotic genes. Additionally, the regulation of anti-oxidant genes were up-regulated especially thioredoxin, glutathione and superoxide dismutase- related genes. Moreover, the treatment also induced the activation of pro-survival heat shock proteins. Collectively, Isopimara-7,15-Dien-19-Oic Acid managed to induce cellular stress in HeLa cells and activate several anti- and pro survival pathways.
  17. Apoptosis and metastasis inhibitory potential of pineapple vinegar against mouse mammary gland cells in vitro and in vivo
    Mohamad NE, Abu N, Yeap SK, Lim KL, Romli MF, Sharifuddin SA, et al.
    Nutr Metab (Lond), 2019;16:49.
    PMID: 31372176 DOI: 10.1186/s12986-019-0380-5
    Background: Plant-based food medicine and functional foods have been consumed extensively due to their bioactive substances and health-beneficial effects. Vinegar is one of them due to its bioactivities, which confers benefits on human body. Our previous study has produced pineapple vinegar that is rich in gallic acid and caffeic acid via 2 steps fermentation. There are many evidences that show the effectiveness of these resources in inhibiting the proliferation and metastasis of the cancer cells through several mechanisms.

    Methods: Freeze-dried pineapple vinegar was evaluated for its in vitro apoptosis and metastasis inhibitory potential using MTT, cell cycle, Annexin V and scratch assays. The in vivo test using BALB/c mice challenged with 4 T1 cells was further investigated by pre-treating the mice with 0.08 or 2 ml/kg body weight of freshly-prepared pineapple vinegar for 28 days. The tumor weight, apoptotic state of cells in tumor, metastasis and immune response of the untreated and pineapple vinegar treatment group were evaluated and compared.

    Results: From the in vitro study, an IC50 value of 0.25 mg/mL after 48 h of treatment was established. Annexin V/PI and scratch closure assays showed that pineapple vinegar induced 70% of cell population to undergo apoptosis and inhibited 30% of wound closure of 4 T1 cells. High concentration of pineapple vinegar (2 ml/kg body weight) led to the reduction of tumor weight and volume by 45%as compared to the untreated 4 T1-challenged mice. This effect might have been contributed by the increase of T cell and NK cells population associated with the overexpression of IL-2 andIFN-γ cytokines and splenocyte cytotoxicity. Furthermore, fewer instances of metastasis events were recorded in the pineapple vinegar treatment group and this could be explained by the downregulation of inflammation related genes (iNOS, NF-kB and COX2), metastasis related genes (iCAM, VEGF and MMP9) and angeogenesis related genes (CD26, TIMP1, HGF, MMP3, IGFBP-1 and IGFBP-2).

    Conclusion: The ability of pineapple vinegar to delay cancer progression portrayed its potential as chemopreventive dietry intervention for cancer therapy.

  18. Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index
    Abu N, Othman N, Ab Razak NS, Bakarurraini NAAR, Nasir SN, Soh JEC, et al.
    Front Cell Dev Biol, 2020;8:564648.
    PMID: 33324632 DOI: 10.3389/fcell.2020.564648
    Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.
  19. Identification of differentially expressed circular RNAs in chemoresistant colorectal cancer
    Abu N, Hon KW, Jeyaraman S, Yahaya A, Abdullah NM, Mustangin M, et al.
    Epigenomics, 2019 06;11(8):875-884.
    PMID: 31020847 DOI: 10.2217/epi-2019-0042
    Aim: Chemoresistance in colorectal cancer (CRC) has become a burden in treating the disease effectively. Circular RNAs (circRNAs) are a type of noncoding RNA that were found to be important in cellular homeostasis. The involvement of circRNAs in relation to chemoresistance in other types of cancers has also been reported. This study aims to identify the differentially expressed circRNAs between chemoresistant and chemosensitive CRC cells. Materials & methods: We developed a chemoresistant cell line model and profiled the circRNAs via microarray. We further validated the expression of two circRNAs in 25 formalin-fixed paraffin-embedded (FFPE) tissue specimens (13 nonresponders and 12 responders) via quantitative polymerase chain reaction (qPCR).  Results & conclusion: We found that there were 773 upregulated and 732 downregulated circRNAs between the chemoresistant and chemosensitive HCT-116 cells. We found that hsa_circ_32883 could be a promising biotarget.
  20. Fulltext Antitumor and Anti-Metastatic Effects of Citral-Loaded Nanostructured Lipid Carrier in 4T1-Induced Breast Cancer Mouse Model
    Nordin N, Yeap SK, Rahman HS, Zamberi NR, Mohamad NE, Abu N, et al.
    Molecules, 2020 Jun 09;25(11).
    PMID: 32526880 DOI: 10.3390/molecules25112670
    Cancer nano-therapy has been progressing rapidly with the introduction of many novel drug delivery systems. The previous study has reported on the in vitro cytotoxicity of citral-loaded nanostructured lipid carrier (NLC-Citral) on MDA-MB-231 cells and some preliminary in vivo antitumor effects on 4T1 breast cancer cells challenged mice. However, the in vivo apoptosis induction and anti-metastatic effects of NLC-Citral have yet to be reported. In this study, the in vitro cytotoxic, anti-migration, and anti-invasion effects of NLC-Citral were tested on 4T1 breast cancer cells. In addition, the in vivo antitumor effects of oral delivery of NLC-Citral was also evaluated on BALB/c mice induced with 4T1 cells. In vitro cytotoxicity results showed that NLC-Citral and citral gave similar IC50 values on 4T1 cells. However, wound healing, migration, and invasion assays reflected better in vitro anti-metastasis potential for NLC-Citral than citral alone. Results from the in vivo study indicated that both NLC-Citral and citral have anti-tumor and anti-metastasis effects, whereby the NLC-Citral showed better efficacy than citral in all experiments. Also, the delay of tumor progression was through the suppression of the c-myc gene expression and induction of apoptosis in the tumor. In addition, the inhibition of metastasis of 4T1 cells to lung and bone marrow by the NLC-Citral and citral treatments was correlated with the downregulation of metastasis-related genes expression including MMP-9, ICAM, iNOS, and NF-kB and the angiogenesis-related proteins including G-CSF alpha, Eotaxin, bFGF, VEGF, IL-1alpha, and M-CSF in the tumor. Moreover, NLC-Citral showed greater downregulation of MMP-9, iNOS, ICAM, Eotaxin, bFGF, VEGF, and M-CSF than citral treatment in the 4T1-challenged mice, which may contribute to the better anti-metastatic effect of the encapsulated citral. This study suggests that NLC is a potential and effective delivery system for citral to target triple-negative breast cancer.
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