Displaying publications 81 - 100 of 140 in total

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  1. Fulltext Cycloart-24-ene-26-ol-3-one, a New Cycloartane Isolated from Leaves of Aglaia exima Triggers Tumour Necrosis Factor-Receptor 1-Mediated Caspase-Dependent Apoptosis in Colon Cancer Cell Line
    Leong KH, Looi CY, Loong XM, Cheah FK, Supratman U, Litaudon M, et al.
    PLoS One, 2016;11(4):e0152652.
    PMID: 27070314 DOI: 10.1371/journal.pone.0152652
    Plants in the Meliaceae family are known to possess interesting biological activities, such as antimalaral, antihypertensive and antitumour activities. Previously, our group reported the plant-derived compound cycloart-24-ene-26-ol-3-one isolated from the hexane extracts of Aglaia exima leaves, which shows cytotoxicity towards various cancer cell lines, in particular, colon cancer cell lines. In this report, we further demonstrate that cycloart-24-ene-26-ol-3-one, from here forth known as cycloartane, reduces the viability of the colon cancer cell lines HT-29 and CaCO-2 in a dose- and time-dependent manner. Further elucidation of the compound's mechanism showed that it binds to tumour necrosis factor-receptor 1 (TNF-R1) leading to the initiation of caspase-8 and, through the activation of Bid, in the activation of caspase-9. This activity causes a reduction in mitochondrial membrane potential (MMP) and the release of cytochrome-C. The activation of caspase-8 and -9 both act to commit the cancer cells to apoptosis through downstream caspase-3/7 activation, PARP cleavage and the lack of NFkB translocation into the nucleus. A molecular docking study showed that the cycloartane binds to the receptor through a hydrophobic interaction with cysteine-96 and hydrogen bonds with lysine-75 and -132. The results show that further development of the cycloartane as an anti-cancer drug is worthwhile.
    Matched MeSH terms: HT29 Cells
  2. Cyclopenta[b]benzofuran and Secodammarane Derivatives from the Stems of Aglaia stellatopilosa
    Othman N, Pan L, Mejin M, Voong JC, Chai HB, Pannell CM, et al.
    J Nat Prod, 2016 Apr 22;79(4):784-91.
    PMID: 26974604 DOI: 10.1021/acs.jnatprod.5b00810
    Four new 2,3-secodammarane triterpenoids, stellatonins A-D (3-6), together with a new 3,4-secodammarane triterpenoid, stellatonin E (7), and the known silvestrol (1), 5‴-episilvestrol (2), and β-sitosterol, were isolated from a methanol extract of the stems of Aglaia stellatopilosa through bioassay-guided fractionation. The structures of the new compounds were elucidated using spectroscopic and chemical methods. The compounds were evaluated for their cytotoxic activity against three human cancer cell lines and for their antimicrobial activity using a microtiter plate assay against a panel of Gram-positive and Gram-negative bacteria and fungi.
    Matched MeSH terms: HT29 Cells
  3. Fulltext γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells
    Yusof KM, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ
    Molecules, 2015 Jun 03;20(6):10280-97.
    PMID: 26046324 DOI: 10.3390/molecules200610280
    Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.
    Matched MeSH terms: HT29 Cells
  4. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery
    Ma Y, Fuchs AV, Boase NR, Rolfe BE, Coombes AG, Thurecht KJ
    Eur J Pharm Biopharm, 2015 Aug;94:393-403.
    PMID: 26117186 DOI: 10.1016/j.ejpb.2015.06.014
    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.
    Matched MeSH terms: HT29 Cells
  5. Water extract of brewers' rice induces antiproliferation of human colorectal cancer (HT-29) cell lines via the induction of apoptosis
    Tan BL, Norhaizan ME, Yeap SK, Roselina K
    Eur Rev Med Pharmacol Sci, 2015;19(6):1022-9.
    PMID: 25855928
    Brewers' rice, a mixture of broken rice, rice bran, and rice germ, is a rice by-product in the rice industry. The present study was designed to investigate the in vitro cytotoxicity of the water extract of brewers' rice (WBR) against colorectal cancer (HT-29) cells.
    Matched MeSH terms: HT29 Cells
  6. Ibogan, tacaman, and cytotoxic bisindole alkaloids from tabernaemontana. Cononusine, an iboga alkaloid with unusual incorporation of a pyrrolidone moiety
    Lim KH, Raja VJ, Bradshaw TD, Lim SH, Low YY, Kam TS
    J Nat Prod, 2015 May 22;78(5):1129-38.
    PMID: 25919190 DOI: 10.1021/acs.jnatprod.5b00117
    Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga-pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N(4)-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 μM). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70-4.19 μM). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.
    Matched MeSH terms: HT29 Cells
  7. Fulltext Group B adenovirus enadenotucirev infects polarised colorectal cancer cells efficiently from the basolateral surface expected to be encountered during intravenous delivery to treat disseminated cancer
    Chia SL, Lei J, Ferguson DJP, Dyer A, Fisher KD, Seymour LW
    Virology, 2017 05;505:162-171.
    PMID: 28260622 DOI: 10.1016/j.virol.2017.02.011
    Enadenotucirev (EnAd) is a group B oncolytic adenovirus developed for systemic delivery and currently undergoing clinical evaluation for advanced cancer therapy. For differentiated carcinomas, systemic delivery would likely expose virus particles to the basolateral surface of cancer cells rather than the apical surface encountered during natural infection. Here, we compare the ability of EnAd and adenovirus type-5 (Ad5) to infect polarised colorectal carcinoma cells from the apical or basolateral surfaces. Whereas Ad5 infection was more efficient via the apical than basolateral surface, EnAd readily infected cells from either surface. Progeny particles from EnAd were released preferentially via the apical surface for all cell lines and routes of infection. These data further support the utility of group B adenoviruses for systemic delivery and suggest that progeny virus are more likely to be released into the tumour rather than back through the basolateral surface into the blood stream.
    Matched MeSH terms: HT29 Cells
  8. Fulltext Establishment of in vitro and in vivo anti-colon cancer efficacy of essential oils containing oleo-gum resin extract of Mesua ferrea
    Asif M, Yehya AHS, Dahham SS, Mohamed SK, Shafaei A, Ezzat MO, et al.
    Biomed Pharmacother, 2019 Jan;109:1620-1629.
    PMID: 30551416 DOI: 10.1016/j.biopha.2018.10.127
    Proven the great potential of essential oils as anticancer agents, the current study intended to explore molecular mechanisms responsible for in vitro and in vivo anti-colon cancer efficacy of essential oil containing oleo-gum resin extract (RH) of Mesua ferrea. MTT cell viability studies showed that RH had broad spectrum cytotoxic activities. However, it induced more profound growth inhibitory effects towards two human colon cancer cell lines i.e., HCT 116 and LIM1215 with an IC50 values of 17.38 ± 0.92 and 18.86 ± 0.80 μg/mL respectively. RH induced relatively less toxicity in normal human colon fibroblasts i.e., CCD-18co. Cell death studies conducted, revealed that RH induced characteristic morphological and biochemical changes in HCT 116. At protein level it down-regulated expression of multiple pro-survival proteins i.e., survivin, xIAP, HSP27, HSP60 and HSP70 and up-regulated expression of ROS, caspase-3/7 and TRAIL-R2 in HCT 116. Furthermore, significant reduction in invasion, migration and colony formation potential was observed in HCT 116 treated with RH. Chemical characterization by GC-MS and HPLC methods revealed isoledene and elemene as one the major compounds. RH showed potent antitumor activity in xenograft model. Overall, these findings suggest that RH holds a promise to be further studied for cheap anti-colon cancer naturaceutical development.
    Matched MeSH terms: HT29 Cells
  9. Fulltext Induction of Apoptosis and Cytotoxicity by Isothiocyanate Sulforaphene in Human Hepatocarcinoma HepG2 Cells
    Kntayya SB, Ibrahim MD, Mohd Ain N, Iori R, Ioannides C, Abdull Razis AF
    Nutrients, 2018 Jun 04;10(6).
    PMID: 29866995 DOI: 10.3390/nu10060718
    Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G₀/G₁ phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.
    Matched MeSH terms: HT29 Cells
  10. Fulltext Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro
    Rahim NFC, Hussin Y, Aziz MNM, Mohamad NE, Yeap SK, Masarudin MJ, et al.
    Molecules, 2021 Feb 26;26(5).
    PMID: 33652694 DOI: 10.3390/molecules26051261
    Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012-2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.
    Matched MeSH terms: HT29 Cells
  11. Fulltext Preparation, characterization and therapeutic properties of gum arabic-stabilized gallic acid nanoparticles
    Hassani A, Azarian MMS, Ibrahim WN, Hussain SA
    Sci Rep, 2020 10 20;10(1):17808.
    PMID: 33082415 DOI: 10.1038/s41598-020-71175-8
    Gallic acid (GA) is a natural phenolic compound with therapeutic effects that are often challenged by its rapid metabolism and clearance. Therefore,  GA was encapsulated using gum arabic into nanoparticles to increase its bioavailability. The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. The GANPs were further evaluated for the in vitro cytotoxicity, cell uptake and cell migration in four types of human cancer cell lines including (MCF-7, MDA-MB231) breast adenocarcinoma, HepG2 hepatocellular cancer, HT-29 colorectal adenocarcinoma, and MCF-10A breast epithelial cell lines. The GANPs demonstrated potent antioxidant effects and have shown promising anti-cancer properties in a dose-dependent manner with a predilection toward HepG2 and MCF7 cancer cells. The uptake of GANPs was successful in the majority of cancer cells with a propensity to accumulate in the nuclear region of the cells. The HepG2 and MCF7 cancer cells also had a significantly higher percentage of apoptosis and were more sensitive to gallic acid nanoparticle treatment in the cell migration assay. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing  the antioxidant properties. The formulated nanoparticles also had remarkably low toxicity in normal cells. Based on these findings, GANPs may have promising therapeutic applications towards the development of more effective treatments with a probable targeting precision in cancer cells.
    Matched MeSH terms: HT29 Cells
  12. Fulltext Events associated with apoptotic effect of p-Coumaric acid in HCT-15 colon cancer cells
    Jaganathan SK, Supriyanto E, Mandal M
    World J Gastroenterol, 2013 Nov 21;19(43):7726-34.
    PMID: 24282361 DOI: 10.3748/wjg.v19.i43.7726
    AIM: To investigate the events associated with the apoptotic effect of p-Coumaric acid, one of the phenolic components of honey, in human colorectal carcinoma (HCT-15) cells.

    METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium-bromide assay was performed to determine the antiproliferative effect of p-Coumaric acid against colon cancer cells. Colony forming assay was conducted to quantify the colony inhibition in HCT 15 and HT 29 colon cancer cells after p-Coumaric acid treatment. Propidium Iodide staining of the HCT 15 cells using flow cytometry was done to study the changes in the cell cycle of treated cells. Identification of apoptosis was done using scanning electron microscope and photomicrograph evaluation of HCT 15 cells after exposing to p-Coumaric acid. Levels of reactive oxygen species (ROS) of HCT 15 cells exposed to p-Coumaric acid was evaluated using 2', 7'-dichlorfluorescein-diacetate. Mitochondrial membrane potential of HCT-15 was assessed using rhodamine-123 with the help of flow cytometry. Lipid layer breaks associated with p-Coumaric acid treatment was quantified using the dye merocyanine 540. Apoptosis was confirmed and quantified using flow cytometric analysis of HCT 15 cells subjected to p-Coumaric acid treatment after staining with YO-PRO-1.

    RESULTS: Antiproliferative test showed p-Coumaric acid has an inhibitory effect on HCT 15 and HT 29 cells with an IC₅₀ (concentration for 50% inhibition) value of 1400 and 1600 μmol/L respectively. Colony forming assay revealed the time-dependent inhibition of HCT 15 and HT 29 cells subjected to p-Coumaric acid treatment. Propidium iodide staining of treated HCT 15 cells showed increasing accumulation of apoptotic cells (37.45 ± 1.98 vs 1.07 ± 1.01) at sub-G1 phase of the cell cycle after p-Coumaric acid treatment. HCT-15 cells observed with photomicrograph and scanning electron microscope showed the signs of apoptosis like blebbing and shrinkage after p-Coumaric acid exposure. Evaluation of the lipid layer showed increasing lipid layer breaks was associated with the growth inhibition of p-Coumaric acid. A fall in mitochondrial membrane potential and increasing ROS generation was observed in the p-Coumaric acid treated cells. Further apoptosis evaluated by YO-PRO-1 staining also showed the time-dependent increase of apoptotic cells after treatment.

    CONCLUSION: These results depicted that p-Coumaric acid inhibited the growth of colon cancer cells by inducing apoptosis through ROS-mitochondrial pathway.

    Matched MeSH terms: HT29 Cells
  13. Heterogeneity in cancer cells: variation in drug response in different primary and secondary colorectal cancer cell lines in vitro
    Arul M, Roslani AC, Cheah SH
    In Vitro Cell Dev Biol Anim, 2017 May;53(5):435-447.
    PMID: 28120247 DOI: 10.1007/s11626-016-0126-x
    Tumor heterogeneity may give rise to differential responses to chemotherapy drugs. Therefore, unraveling tumor heterogeneity has an implication for biomarker discovery and cancer therapeutics. To test this phenomenon, we investigated the differential responses of three secondary colorectal cancer cell lines of different origins (HCT116, HT29, and SW620 cells) and four novel primary cell lines obtained from different colorectal cancer patients to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) and explored the differences in gene expression among the primary cell lines in response to exposure to cytotoxic drugs. Cells were exposed to different doses of 5-FU and L-OHP separately or in combinations of equitoxic drug or equimolar drug ratios (median effect of Chou-Talalay principle). Cell viability was assessed using MTT assay and the respective IC50values were determined. Changes in gene expression in primary cell lines after exposure to the same drug doses were compared using real-time PCR array. The sensitivities (IC50) of different cell lines, both secondary and primary, to 5-FU and L-OHP were significantly different, whether in monotherapy or combined treatment. Primary cell lines needed higher doses to reach IC50. There were variations in gene expression among the primary cell lines of different chemosensitivities to the challenge of the same combined dose of 5-FU and L-OHP. The results confirm the heterogeneous nature of colorectal cancer cells from different patient tumors. Studies using primary cancer cells established from patient's tumors rather than secondary cell lines will more closely reflect the actual character of the disease.
    Matched MeSH terms: HT29 Cells
  14. Fulltext Clausenidin induces caspase-dependent apoptosis in colon cancer
    Waziri PM, Abdullah R, Yeap SK, Omar AR, Kassim NK, Malami I, et al.
    BMC Complement Altern Med, 2016 Jul 29;16:256.
    PMID: 27473055 DOI: 10.1186/s12906-016-1247-1
    BACKGROUND: Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. The main bioactive chemical components of the plant are alkaloids and coumarins. In this study, we isolated clausenidin from the roots of C. excavata to determine its apoptotic effect on the colon cancer (HT-29) cell line.
    METHOD: We examined the effect of clausenidin on cell viability, ROS generation, DNA fragmentation, mitochondrial membrane potential in HT-29 cells. Ultrastructural analysis was conducted for morphological evidence of apoptosis in the treated HT-29 cells. In addition, we also evaluated the effect of clausenidin treatment on the expression of caspase 3 and 9 genes and proteins in HT-29 cells.
    RESULT: Clausenidin induced a G0/G1 cell cycle arrest in HT-29 cells with significant (p 
    Matched MeSH terms: HT29 Cells
  15. Fulltext Hypolipidemic activities of xanthorrhizol purified from centrifugal TLC
    Oon SF, Nallappan M, Kassim NK, Shohaimi S, Sa'ariwijaya MS, Tee TT, et al.
    Biochem Biophys Res Commun, 2016 09 23;478(3):1403-8.
    PMID: 27576204 DOI: 10.1016/j.bbrc.2016.08.136
    Hyperlipidemia is defined as the presence of either hypertriglyceridemia or hypercholesterolemia, which could cause atherosclerosis. Although hyperlipidemia can be treated by hypolipidemic drugs, they are limited due to lack of effectiveness and safety. Previous studies demonstrated that xanthorrhizol (XNT) isolated from Curcuma xanthorrhizza Roxb. reduced the levels of free fatty acid and triglyceride in vivo. However, its ability to inhibit cholesterol uptake in HT29 colon cells and adipogenesis in 3T3-L1 cells are yet to be reported. In this study, XNT purified from centrifugal TLC demonstrated 98.3% purity, indicating it could be an alternative purification method. The IC50 values of XNT were 30.81 ± 0.78 μg/mL in HT29 cells and 35.07 ± 0.24 μg/mL in 3T3-L1 adipocytes, respectively. Cholesterol uptake inhibition study using HT29 colon cells showed that XNT (15 μg/mL) significantly inhibited the fluorescent cholesterol analogue NBD uptake by up to 27 ± 3.1% relative to control. On the other hand, higher concentration of XNT (50 μg/mL) significantly suppressed the growth of 3T3-L1 adipocytes (5.9 ± 0.58%) compared to 3T3-L1 preadipocytes (81.31 ± 0.55%). XNT was found to impede adipogenesis of 3T3-L1 adipocytes in a dose-dependent manner from 3.125 to 12.5 μg/mL, where 12.5 μg/mL significantly suppressed 36.13 ± 2.1% of lipid accumulation. We postulate that inhibition of cholesterol uptake, adipogenesis, preadipocyte and adipocyte number may be utilized as treatment modalities to reduce the prevalence of lipidemia. To conclude, XNT could be a potential hypolipidemic agent to improve cardiovascular health in the future.
    Matched MeSH terms: HT29 Cells
  16. Fulltext pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery
    Biabanikhankahdani R, Alitheen NBM, Ho KL, Tan WS
    Sci Rep, 2016 11 24;6:37891.
    PMID: 27883070 DOI: 10.1038/srep37891
    Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
    Matched MeSH terms: HT29 Cells
  17. Analysis of chemical constituents, antimicrobial and anticancer activities of dichloromethane extracts of Sordariomycetes sp. endophytic fungi isolated from Strobilanthes crispus
    Jinfeng EC, Mohamad Rafi MI, Chai Hoon K, Kok Lian H, Yoke Kqueen C
    World J Microbiol Biotechnol, 2017 Jan;33(1):5.
    PMID: 27844243
    Plants are primary source of natural product drugs. However, with every new bioactive molecule reported from a plant source, there follows reports of endangered status or even extinction of a medicinally important plant due to over-harvesting. Hence, the attention turned towards fungi namely the endophytes, which reside within medicinally important plants and thus may have acquired their medicinal properties. Strobilanthes crispus is a traditional medicinal plant which has been used traditionally to treat kidney stones, diabetes, hypertension and cancer as well as having antimicrobial activities. In our efforts to bioprospect for anticancer and antimicrobial metabolites, two fungal endophytes most closely related to the Sordariomycetes sp. showed promising results. Sample (PDA)BL3 showed highest significant antimicrobial activity against 6 bacteria at 200 µg/disc whereas sample (PDA)BL5 has highest significant anticancer activity against all 5 cancer cell lines at concentrations ranging from 30 to 300 μg/ml. As for the gas chromatography coupled with mass spectrometry (GC-MS) results, a total of 20 volatile metabolites identified from sample (PDA)BL3 and 21 volatile metabolites identified from sample (PDA)BL5 having more than 1% abundance. Both GC-MS analysis showed that compound Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) has the highest abundance at 15.10% abundance for sample (PDA)BL3 and 19.00% abundance for sample (PDA)BL5 respectively. In conclusion, these results have shown bio-prospecting potential of endophytic fungi having antimicrobial and anticancer activities as well as its potential secondary metabolites of interest. Therefore, this work has further indicated the medicinal and industrial potential of endophytic fungi.
    Matched MeSH terms: HT29 Cells
  18. Improvement of physicochemical properties of nanocolloidal carrier loaded with low water solubility drug for parenteral cancer treatment by Response Surface Methodology
    Izadiyan Z, Basri M, Fard Masoumi HR, Abedi Karjiban R, Salim N, Kalantari K
    Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:841-849.
    PMID: 30423770 DOI: 10.1016/j.msec.2018.10.015
    Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ± 2 °C, 25 ± 2 °C and 45 ± 2 °C).
    Matched MeSH terms: HT29 Cells
  19. Antifungal and Mucoadhesive Properties of an Orally Administered Chitosan-Coated Amphotericin B Nanostructured Lipid Carrier (NLC)
    Ling JTS, Roberts CJ, Billa N
    AAPS PharmSciTech, 2019 Mar 05;20(3):136.
    PMID: 30838459 DOI: 10.1208/s12249-019-1346-7
    Surface-modified nanostructured lipid carriers (NLC) represent a promising mode of drug delivery used to enhance retention of drugs at absorption site. Formulated chitosan-coated amphotericin-B-loaded NLC (ChiAmp NLC) had a size of 394.4 ± 6.4 nm, encapsulation and loading efficiencies of 86.0 ± 3% and 11.0 ± 0.1% respectively. Amphotericin-B release from NLCs was biphasic with no changes in physical properties upon exposure to simulated gastrointestinal conditions. Antifungal properties of Amphotericin-B and ChiAmpB NLC were comparable but ChiAmpB NLC was twice less toxic to red blood cells and ten times safer on HT-29 cell lines. In vitro mucoadhesion data were observed ex vivo, where ChiAmpB NLC resulted in higher retention within the small intestine compared to the uncoated formulation. The data strongly offers the possibility of orally administering a non-toxic, yet effective Amphotericin-B nanoformulation for the treatment of systemic fungal infections.
    Matched MeSH terms: HT29 Cells
  20. Novel 2-Benzoyl-6-(2,3-Dimethoxybenzylidene)-Cyclohexenol Confers Selectivity toward Human MLH1 Defective Cancer Cells through Synthetic Lethality
    Song DSS, Leong SW, Ng KW, Abas F, Shaari K, Leong CO, et al.
    SLAS Discov, 2019 06;24(5):548-562.
    PMID: 30897027 DOI: 10.1177/2472555219831405
    DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency.
    Matched MeSH terms: HT29 Cells
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