Displaying publications 41 - 60 of 145 in total

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  1. Fulltext Phenolic content, antioxidant effect and cytotoxic activity of Leea indica leaves
    Reddy NS, Navanesan S, Sinniah SK, Wahab NA, Sim KS
    BMC Complement Altern Med, 2012 Aug 17;12:128.
    PMID: 22898370 DOI: 10.1186/1472-6882-12-128
    BACKGROUND: The leaves of Leea indica (Vitaceae), commonly known as 'Huo Tong Shu' in Malaysia, have been traditionally used as natural remedy in folk medicine by the locals. The current study reports the outcome of antioxidant and cytotoxic investigation of L. indica leaves. To the best of our knowledge, this is the first report of L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) for evaluation of total phenolic content, antioxidant effect and cytotoxic activity against colon cancer cell lines.

    METHODS: In the present study, L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) were firstly prepared prior to phenolic content, antioxidant effect and cytotoxic activity assessment. Folin-Ciocalteau's method was used for the measurement of total phenolic content of the extracts. The antioxidant activity was measured by employing three different established testing systems, such as scavenging activity on DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, reducing power assay and SOD (superoxide dismutase) activity assay. The cytotoxic activity of the extracts were evaluated against three colon cancer cell lines with varying molecular characteristics (HT-29, HCT-15 and HCT-116) by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay.

    RESULTS: The total phenolic content and antioxidant capabilities differed significantly among the L. indica leaf extracts. A strong correlation between total phenolic content and antioxidant properties was found, indicating that phenolic compounds are the major contributor to the antioxidant properties of these extracts. Among the crude ethanol and its fractionated extracts, fractionated water extract showed significantly the highest total phenolic content and strongest antioxidant effect in all the antioxidant testing systems employed in this study. All the four extracts exert no damage to the selected colon cancer cells.

    CONCLUSIONS: The data obtained in these testing systems clearly establish the antioxidant potency of the fractionated water extract of L. indica leaves. Additional studies should be carried out to isolate and identify the bioactive compounds in the fractionated water extract, in order to provide more convincing evidence.

    Matched MeSH terms: HT29 Cells
  2. Effect of organic-phase solvents on physicochemical properties and cellular uptake of astaxanthin nanodispersions
    Anarjan N, Tan CP, Ling TC, Lye KL, Malmiri HJ, Nehdi IA, et al.
    J Agric Food Chem, 2011 Aug 24;59(16):8733-41.
    PMID: 21726079 DOI: 10.1021/jf201314u
    A simplex centroid mixture design was used to study the interactions between two chosen solvents, dichloromethane (DCM) and acetone (ACT), as organic-phase components in the formation and physicochemical characterization and cellular uptake of astaxanthin nanodispersions produced using precipitation and condensation processes. Full cubic or quadratic regression models with acceptable determination coefficients were obtained for all of the studied responses. Multiple-response optimization predicted that the organic phase with 38% (w/w) DCM and 62% (w/w) ACT yielded astaxanthin nanodispersions with the minimum particle size (106 nm), polydispersity index (0.191), and total astaxanthin loss (12.7%, w/w) and the maximum cellular uptake (2981 fmol/cell). Astaxanthin cellular uptake from the produced nanodispersions also showed a good correlation with their particle size distributions and astaxanthin trans/cis isomerization ratios. The absence of significant (p > 0.05) differences between the experimental and predicted values of the response variables confirmed the adequacy of the fitted models.
    Matched MeSH terms: HT29 Cells
  3. Challenges associated with the synthesis of unusual o-carboxamido stilbenes by the Heck protocol: Intriguing substituent effects, their toxicological and chemopreventive implications
    Kee CH, Ariffin A, Awang K, Takeya K, Morita H, Hussain SI, et al.
    Org Biomol Chem, 2010 Dec 21;8(24):5646-60.
    PMID: 20941451 DOI: 10.1039/c0ob00296h
    The syntheses of fourteen unusual o-carboxamido stilbenes by the Heck protocol revealed surprising complexity related to intriguing substituent effects with mechanistic implications. The unexpected cytotoxic and chemopreventive properties also seem to be substituent dependent. For example, although stilbene 15d (with a 4-methoxy substituent) showed cytotoxicity on HT29 colon cancer cells with an IC(50) of 4.9 μM, the 3,4-dimethoxy derivative (15c) is inactive. It is interesting to observe that the 3,5-dimethoxy derivative (15e) showed remarkable chemopreventive activity in WRL-68 fetal hepatocytes, surpassing the gold standard, resveratrol. The resveratrol concentration needed to be 5 times higher than that of 15e to produce comparable elevation of NQO1.
    Matched MeSH terms: HT29 Cells
  4. RNA Sequencing and Bioinformatics Analysis Reveals the Downregulation of DNA Replication Genes by Morindone in Colorectal Cancer Cells
    Chee CW, Mohd Hashim N, Abdullah I, Nor Rashid N
    Appl Biochem Biotechnol, 2024 Jun;196(6):3216-3233.
    PMID: 37642925 DOI: 10.1007/s12010-023-04690-9
    Morindone, a natural anthraquinone compound, has been reported to have significant pharmacological properties in different cancers. However, its anticancer effects in colorectal cancer (CRC) and the underlying molecular mechanisms remain obscure. In this study, RNA sequencing was used to assess the differentially expressed genes (DEGs) following morindone treatment in two CRC cell lines, HCT116 and HT29 cells. Functional enrichment analysis of overlapping DEGs revealed that negative regulation of cell development from biological processes and the MAPK signalling pathway were the most significant Gene Ontology terms and Kyoto Encyclopaedia of Genes and Genome pathway, respectively. Seven hub genes were identified among the overlapping genes, including MCM5, MCM6, MCM10, GINS2, POLE2, PRIM1, and WDHD1. All hub genes were found downregulated and involved in DNA replication fork. Among these, GINS2 was identified as the most cancer-dependent gene in both cells with better survival outcomes. Validation was performed on seven hub genes with rt-qPCR, and the results were consistent with the RNA sequencing findings. Collectively, this study provides corroboration of the potential therapeutic benefits and suitable pharmacological targets of morindone in the treatment of CRC.
    Matched MeSH terms: HT29 Cells
  5. Fulltext Isolation, Characterization, Crystal Structure Elucidation, and Anticancer Study of Dimethyl Cardamonin, Isolated from Syzygium campanulatum Korth
    Memon AH, Ismail Z, Aisha AF, Al-Suede FS, Hamil MS, Hashim S, et al.
    Evid Based Complement Alternat Med, 2014;2014:470179.
    PMID: 25530783 DOI: 10.1155/2014/470179
    Syzygium campanulatum Korth is an equatorial, evergreen, aboriginal shrub of Malaysia. Conventionally it has been used as a stomachic. However, in the currently conducted study dimethyl cardamonin or 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) was isolated from S. campanulatum Korth, leaf extract. The structural characterization of DMC was carried out by making use of various techniques including UV, IR, NMR spectral followed by LC-MS, and X-ray crystallographic techniques. For determining the purity of compound, highly effective techniques including TLC, HPLC, and melting point were used. The cytotoxicity of DMC and three different extracts of S. campanulatum was evaluated against human colon cancer cell line (HT-29) by three different assays. DMC and ethanolic extract revealed potent and dose-dependent cytotoxic activity on the cancer cell line with IC50 12.6 and 90.1 µg/mL, respectively. Quite astonishingly to our knowledge, this is the very first report on S. campanulatum as being a rich source (3.5%) of DMC, X-ray crystallography, and anticancer activity on human colon cancer cells.
    Matched MeSH terms: HT29 Cells
  6. Fulltext White tea (Camellia sinensis) inhibits proliferation of the colon cancer cell line, HT-29, activates caspases and protects DNA of normal cells against oxidative damage
    Hajiaghaalipour F, Kanthimathi MS, Sanusi J, Rajarajeswaran J
    Food Chem, 2015 Feb 15;169:401-10.
    PMID: 25236244 DOI: 10.1016/j.foodchem.2014.07.005
    Tea (Camellia sinensis) is one of the most consumed beverages in the world. White tea is made from the buds and young leaves of the tea plant which are steamed and dried, whilst undergoing minimal oxidation. The MTT assay was used to test the extract on the effect of the proliferation of the colorectal cancer cell line, HT-29. The extract inhibited the proliferation of HT-29 cells with an IC50 of 87μg/ml. The extract increased the levels of caspase-3, -8, and -9 activity in the cells. DNA damage in 3T3-L1 normal cells was detected by using the comet assay. The extract protected 3T3-L1 cells against H2O2-induced DNA damage. The results from this study show that white tea has antioxidant and antiproliferative effects against cancer cells, but protect normal cells against DNA damage. Regular intake of white tea can help to maintain good health and protect the body against disease.
    Matched MeSH terms: HT29 Cells
  7. Fulltext Kingianic acids A-G, Endiandric acid analogues from Endiandra kingiana
    Azmi MN, Gény C, Leverrier A, Litaudon M, Dumontet V, Birlirakis N, et al.
    Molecules, 2014;19(2):1732-47.
    PMID: 24492595 DOI: 10.3390/molecules19021732
    A phytochemical investigation of the methanolic extract of the bark of Endiandra kingiana led to the isolation of seven new tetracyclic endiandric acid analogues, kingianic acids A-G (1-7), together with endiandric acid M (8), tsangibeilin B (9) and endiandric acid (10). Their structures were determined by 1D- and 2D-NMR analysis in combination with HRMS experiments. The structure of compounds 9 and 10 were confirmed by single-crystal X-ray diffraction analysis. These compounds were screened for Bcl-xL and Mcl-1 binding affinities and cytotoxic activity on various cancer cell lines. Compound 5 showed moderate cytotoxic activity against human colorectal adeno-carcinoma (HT-29) and lung adenocarcinoma epithelial (A549) cell lines, with IC50 values in the range 15-17 µM, and compounds 3, 6 and 9 exhibited weak binding affinity for the anti-apoptotic protein Mcl-1.
    Matched MeSH terms: HT29 Cells
  8. Fulltext Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor
    Teoh WY, Sim KS, Moses Richardson JS, Abdul Wahab N, Hoe SZ
    Evid Based Complement Alternat Med, 2013;2013:958407.
    PMID: 24369485 DOI: 10.1155/2013/958407
    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.
    Matched MeSH terms: HT29 Cells
  9. Fulltext Design, synthesis and cytotoxic evaluation of o-carboxamido stilbene analogues
    Azmi MN, Din MF, Kee CH, Suhaimi M, Ping AK, Ahmad K, et al.
    Int J Mol Sci, 2013;14(12):23369-89.
    PMID: 24287912 DOI: 10.3390/ijms141223369
    Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50=16.68 µM), colon cancer HT-29 (IC50=7.51 µM) and breast cancer MCF-7 (IC50=21.24 µM), respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.
    Matched MeSH terms: HT29 Cells
  10. Fulltext Colonic targeting insulin-loaded trimethyl chitosan nanoparticles coated pectin for oral delivery: In vitro and In vivo studies
    Seyam S, Choukaife H, Al Rahal O, Alfatama M
    Int J Biol Macromol, 2024 Nov;281(Pt 4):136549.
    PMID: 39401622 DOI: 10.1016/j.ijbiomac.2024.136549
    Colon-targeted delivery offers several benefits for oral protein delivery, such as low proteolytic enzyme activity, a natural pH environment, and extended residence time, which improve the bioavailability of the encapsulated protein. Therefore, we hypothesize that developing a novel colonic nanocarrier system, featuring modified chitosan that is soluble at physiological pH and coated with a colon-degradable polymer, will provide an effective delivery system for oral insulin. This study aims to synthesize insulin-loaded pectin-trimethyl chitosan nanoparticles (Ins-P-TMC-NPs) as an oral insulin delivery system and to evaluate its efficacy both in vitro and in vivo. N-trimethyl chitosan (TMC), synthesized via a methylation method, was used to prepare insulin-TMC nanoparticles coated with pectin via the ionic gelation method. The nanoparticles were characterized for their physicochemical properties, cumulative release profile, and surface morphology. The in vitro biological cytotoxicity and cellular uptake of the nanoparticles were evaluated against HT-29 cells. The in vivo blood glucose-lowering effect and histological toxicity were assessed in diabetic male Sprague-Dawley rats. The results showed that Ins-P-TMC-NPs were spherical, with an average size of 379.40 ± 40.26 nm, a polydispersity index of 24.10 ± 1.03 %, a zeta potential of +17.20 ± 0.52 mV, and a loading efficiency of 83.21 ± 1.23 %. Compared to uncoated TMC nanoparticles, Ins-P-TMC-NPs reduced insulin loss in simulated gastrointestinal fluid by approximately 67.23 ± 0.97 % and provided controlled insulin release in simulated colonic fluid. In vitro bioactivity studies revealed that Ins-P-TMC-NPs were non-toxic, with cell viability of 91.12 ± 0.91 % after 24 h of treatment, and exhibited high cellular uptake in the HT-29 cell line with a fluorescence intensity of 37.80 ± 2.40 after 4 h of incubation. Furthermore, the in vivo study demonstrated a sustained reduction in blood glucose levels after oral administration of Ins-P-TMC-NPs, peaking after 8 h with a blood glucose reduction of 87 ± 1.03 %. Histological sections showed no signs of toxicity when compared to those of healthy rats. Overall, the developed colon-targeted oral insulin delivery system exhibits strong potential as a candidate for effective oral insulin administration.
    Matched MeSH terms: HT29 Cells
  11. Fulltext CRISPR/Cas9 mediated ENT2 gene knockout altered purine catabolic pathway and induced apoptosis in colorectal cell lines
    Naes SM, Ab-Rahim S, Mazlan M, Syafruddin SE, Mohtar MA, Abuhamad AY, et al.
    PLoS One, 2025;20(8):e0329501.
    PMID: 40824957 DOI: 10.1371/journal.pone.0329501
    Although purine metabolism is one of the most impacted pathways in colorectal cancer (CRC), little is known about the role of equilibrative nucleoside transporter 2 (ENT2) in CRC development and its association with the altered purine metabolism pathway. This study aimed to determine the role of ENT2 in altered purine metabolism in the early and late stages of CRC using CRISPR/Cas9 gene editing tools and a variety of functional experiments. The expression of ENT2 was significantly higher (P HT29 cells and the late stage DLD1 cells, were knocked out (KO) using the CRISPR/Cas9 tool. The hypoxanthine (HPX) level and the xanthine oxidase (XO) activity were significantly higher in both HT29/KO and DLD1/KO single cell-derived clones (P HT29/KO clonal cells. In this context, targeting ENT2 gene might be a potential strategy in CRC treatment by increasing the production of ROS and hence, inducing the apoptosis pathway.
    Matched MeSH terms: HT29 Cells
  12. Fulltext Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug
    Krishnan P, Rajan M, Kumari S, Sakinah S, Priya SP, Amira F, et al.
    Sci Rep, 2017 09 08;7(1):10962.
    PMID: 28887536 DOI: 10.1038/s41598-017-09140-1
    Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and β-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT's solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.
    Matched MeSH terms: HT29 Cells
  13. Fulltext DK1 Induces Apoptosis via Mitochondria-Dependent Signaling Pathway in Human Colon Carcinoma Cell Lines In Vitro
    Hussin Y, Aziz MNM, Che Rahim NF, Yeap SK, Mohamad NE, Masarudin MJ, et al.
    Int J Mol Sci, 2018 Apr 11;19(4).
    PMID: 29641445 DOI: 10.3390/ijms19041151
    Extensive research has been done in the search for innovative treatments against colon adenocarcinomas; however, the incidence rate of patients remains a major cause of cancer-related deaths in Malaysia. Natural bioactive compounds such as curcumin have been substantially studied as an alternative to anticancer drug therapies and have been surmised as a potent agent but, nevertheless, remain deficient due to its poor cellular uptake. Therefore, efforts now have shifted toward mimicking curcumin to synthesize novel compounds sharing similar effects. A synthetic analog, (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-ene-1-one (DK1), was recently synthesized and reported to confer improved bioavailability and selectivity toward human breast cancer cells. This study, therefore, aims to assess the anticancer mechanism of DK1 in relation to the induction of in vitro cell death in selected human colon cancer cell lines. Using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, the cytotoxicity of DK1 towards HT29 and SW620 cell lines were investigated. Acridine orange/propidium iodide (AO/PI) dual-staining assay and flow cytometry analyses (cell cycle analysis, Annexin/V-FITC and JC-1 assays) were incorporated to determine the mode of cell death. To further determine the mechanism of cell death, quantitative real-time polymerase chain reaction (qRT-PCR) and proteome profiling were conducted. Results from this study suggest that DK1 induced changes in cell morphology, leading to a decrease in cell viability and subsequent induction of apoptosis. DK1 treatment inhibited cell viability and proliferation 48 h post treatment with IC50 values of 7.5 ± 1.6 µM for HT29 cells and 14.5 ± 4.3 µM for SW620 cells, causing cell cycle arrest with increased accumulation of cell populations at the sub-G₀/G₁phaseof 74% and 23%, respectively. Flow cytometry analyses showed that DK1 treatment in cancer cells induced apoptosis, as indicated by DNA fragmentation and depolarization of the mitochondrial membrane. qRT-PCR results show significant upregulation in the expression of caspase-9 in both HT29 and SW620 cell lines, further supporting that cell death induction by DK1 is via an intrinsic pathway. These outcomes, therefore, demonstrate DK1 as a potential anticancer agent for colon adenocarcinoma due to its anti-apoptotic attributes.
    Matched MeSH terms: HT29 Cells
  14. Fulltext Anticancer effect of dentatin and dentatin-hydroxypropyl-β-cyclodextrin complex on human colon cancer (HT-29) cell line
    Al-Abboodi AS, Rasedee A, Abdul AB, Taufiq-Yap YH, Alkaby WAA, Ghaji MS, et al.
    Drug Des Devel Ther, 2017;11:3309-3319.
    PMID: 29200826 DOI: 10.2147/DDDT.S147626
    Introduction: Dentatin (DEN) (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl) dipyran-2-one), a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-β-cyclodextrin (HPβCD) will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HPβCD complex were demonstrated in human colon HT-29 cancer cells.

    Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HPβCD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP-ribose) polymerase, p53, p21, cyclin A as well as the Bcl-2 family of proteins.

    Results: At 3, 6, 12, and 24 µg/mL exposure, DEN and DEN-HPβCD complex significantly affected apoptosis in HT-29 cells through the down-regulation of Bcl-2 and cyclin A in turn, and up-regulation of Bax, p53, p21, cytochrome c at both protein and mRNA levels. DEN and DEN-HPβCD complex also decreased cleaved poly (ADP-ribose) polymerase and induced caspases-3, -8, and -9.

    Conclusion: Results of this study indicate that the apoptotic pathway caused by DEN and DEN-HPβCD complex are mediated by the regulation of caspases and Bcl-2 families in human colon HT-29 cancer cells. The results also suggest that DEN-HPβCD complex may have chemotherapeutic benefits for colon cancer patients.

    Matched MeSH terms: HT29 Cells
  15. 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: HT29 Cells
  16. Biocompatible disulphide cross-linked sodium alginate derivative nanoparticles for oral colon-targeted drug delivery
    Ayub AD, Chiu HI, Mat Yusuf SNA, Abd Kadir E, Ngalim SH, Lim V
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):353-369.
    PMID: 30691309 DOI: 10.1080/21691401.2018.1557672
    The application of layer-by-layer (LbL) approach on nanoparticle surface coating improves the colon-specific drug delivery of insoluble drugs. Here, we aimed to formulate a self-assembled cysteamine-based disulphide cross-linked sodium alginate with LbL self-assembly to improve the delivery of paclitaxel (PCX) to colonic cancer cells. Cysteamine was conjugated to the backbone of oxidized SA to form a core of self-assembled disulphide cross-linked nanospheres. P3DL was selected for PCX loading and fabricated LbL with poly(allylamine hydrochloride) (PAH) and poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSCMA) resulting from characterization and drug release studies. P3DL-fabricated PCX-loaded nanospheres (P3DL/PAH/PSSCMA) exhibited an encapsulation efficiency of 77.1% with cumulative drug release of 45.1%. Dynamic light scattering analysis was reported at 173.6 ± 2.5 nm with polydispersity index of 0.394 ± 0.105 (zeta potential= -58.5 mV). P3DL/PAH/PSSCMA demonstrated a pH-dependent swelling transition; from pH 1 to 7 (102.2% increase). The size increased by 33.0% in reduction response study after incubating with 10 mM glutathione (day 7). HT-29 cells showed high viabilities (86.7%) after treatment with the fabricated nanospheres at 0.8 µg/mL. Cellular internalization was successful with more than 70.0% nanospheres detected in HT-29 cells. Therefore, this fabricated nanospheres may be considered as potential nanocarriers for colon cancer-targeted chemotherapeutic drug delivery.
    Matched MeSH terms: HT29 Cells
  17. Macroline-Sarpagine Bisindole Alkaloids with Antiproliferative Activity from Alstonia penangiana
    Yeap JS, Saad HM, Tan CH, Sim KS, Lim SH, Low YY, et al.
    J Nat Prod, 2019 11 22;82(11):3121-3132.
    PMID: 31642315 DOI: 10.1021/acs.jnatprod.9b00712
    A methanol extract of the stem bark of the Malayan Alstonia penangiana provided seven new bisindole alkaloids, comprising six macroline-sarpagine alkaloids (angustilongines E-K, 1-6) and one macroline-pleiocarpamine bisindole alkaloid (angustilongine L, 7). Analysis of the spectroscopic data (NMR and MS) of these compounds led to the proposed structures of these alkaloids. The macroline-sarpagine alkaloids (1-6) showed in vitro growth inhibitory activity against a panel of human cancer cell lines, inclusive of KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells (IC50 values: 0.02-9.0 μM).
    Matched MeSH terms: HT29 Cells
  18. Fulltext Synthesis of novel cytotoxic tetracyclic acridone derivatives and study of their molecular docking, ADMET, QSAR, bioactivity and protein binding properties
    Veligeti R, Madhu RB, Anireddy J, Pasupuleti VR, Avula VKR, Ethiraj KS, et al.
    Sci Rep, 2020 11 26;10(1):20720.
    PMID: 33244007 DOI: 10.1038/s41598-020-77590-1
    Acridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of tetracyclic acridones with amide framework viz., 3-(alkyloyl/ aryloyl/ heteroaryloyl/ heteroaryl)-2,3-dihydropyrazino[3,2,1-de]acridin-7(1H)-ones and screened for their in vitro anti-cancer activity. The in vitro study revealed that compounds with cyclopropyl-acetyl, benzoyl, p-hydroxybenzoyl, p-(trifluoromethyl)benzoyl, p-fluorobenzoyl, m-fluorobenzoyl, picolinoyl, 6-methylpicolinoyl and 3-nicotinoyl groups are active against HT29, MDAMB231 and HEK293T cancer cell lines. The molecular docking studies performed for them against 4N5Y, HT29 and 2VWD revealed the potential ligand-protein binding interactions among the neutral aminoacid of the enzymes and carbonyl groups of the title compounds with a binding energy ranging from - 8.1394 to - 6.9915 kcal/mol. In addition, the BSA protein binding assay performed for them has confirmed their interaction with target proteins through strong binding to BSA macromolecule. The additional studies like ADMET, QSAR, bioactivity scores, drug properties and toxicity risks ascertained them as newer drug candidates. This study had added a new collection of piperazino fused acridone derivatives to the existing array of other nitrogen heterocyclic fused acridone derivatives as anticancer agents.
    Matched MeSH terms: HT29 Cells
  19. Evaluation of metabolomics behavior of human colon cancer HT29 cell lines treated with ionic liquid graviola fruit pulp extract
    Daddiouaissa D, Amid A, Abdullah Sani MS, Elnour AAM
    J Ethnopharmacol, 2021 Apr 24;270:113813.
    PMID: 33444719 DOI: 10.1016/j.jep.2021.113813
    ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have been used by indigenous people across the world for centuries to help individuals preserve their wellbeing and cure diseases. Annona muricata L. (Graviola) which is belonging to the Annonaceae family has been traditionally used due to its medicinal abilities including antimicrobial, anti-inflammatory, antioxidant and cancer cell growth inhibition. Graviola is claimed to be a potential antitumor due to its selective cytotoxicity against several cancer cell lines. However, the metabolic mechanism information underlying the anticancer activity remains limited.

    AIM OF THE STUDY: This study aimed to investigate the effect of ionic liquid-Graviola fruit pulp extract (IL-GPE) on the metabolomics behavior of colon cancer (HT29) by using an untargeted GC-TOFMS-based metabolic profiling.

    MATERIALS AND METHODS: Multivariate data analysis was used to determine the metabolic profiling, and the ingenuity pathway analysis (IPA) was used to predict the altered canonical pathways after treating the HT29 cells with crude IL-GPE and Taxol (positive control).

    RESULTS: The principal components analysis (PCA) identified 44 metabolites with the most reliable factor loading, and the cluster analysis (CA) separated three groups of metabolites: metabolites specific to the non-treated HT29 cells, metabolites specific to the treated HT29 cells with the crude IL-GPE and metabolites specific to Taxol treatment. Pathway analysis of metabolomic profiles revealed an alteration of many metabolic pathways, including amino acid metabolism, aerobic glycolysis, urea cycle and ketone bodies metabolism that contribute to energy metabolism and cancer cell proliferation.

    CONCLUSION: The crude IL-GPE can be one of the promising anticancer agents due to its selective inhibition of energy metabolism and cancer cell proliferation.

    Matched MeSH terms: HT29 Cells
  20. Fulltext Cudraflavone C Induces Tumor-Specific Apoptosis in Colorectal Cancer Cells through Inhibition of the Phosphoinositide 3-Kinase (PI3K)-AKT Pathway
    Soo HC, Chung FF, Lim KH, Yap VA, Bradshaw TD, Hii LW, et al.
    PLoS One, 2017;12(1):e0170551.
    PMID: 28107519 DOI: 10.1371/journal.pone.0170551
    Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway. Gene expression profiling by microarray analyses revealed that tumor suppressor genes EGR1, HUWE1 and SMG1 were significantly up-regulated while oncogenes such as MYB1, CCNB1 and GPX2 were down-regulated following treatment with Cud C. Further analyses using Connectivity Map revealed that Cud C induced a gene signature highly similar to that of protein synthesis inhibitors and phosphoinositide 3-kinase (PI3K)-AKT inhibitors, suggesting that Cud C might inhibit PI3K-AKT signaling. A luminescent cell free PI3K lipid kinase assay revealed that Cud C significantly inhibited p110β/p85α PI3K activity, followed by p120γ, p110δ/p85α, and p110α/p85α PI3K activities. The inhibition by Cud C on p110β/p85α PI3K activity was comparable to LY-294002, a known PI3K inhibitor. Cud C also inhibited phosphorylation of AKT independent of NFκB activity in CRC cells, while ectopic expression of myristoylated AKT completely abrogated the anti-proliferative effects, and apoptosis induced by Cud C in CRC. These findings demonstrate that Cud C induces tumor-selective cytotoxicity by targeting the PI3K-AKT pathway. These findings provide novel insights into the mechanism of action of Cud C, and indicate that Cud C further development of Cud C derivatives as potential therapeutic agents is warranted.
    Matched MeSH terms: HT29 Cells
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