Displaying publications 1 - 20 of 41 in total

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  1. Fulltext Senescence affects endothelial cells susceptibility to dengue virus infection
    AbuBakar S, Shu MH, Johari J, Wong PF
    Int J Med Sci, 2014;11(6):538-44.
    PMID: 24782642 DOI: 10.7150/ijms.7896
    Alteration in the endothelium leading to increased vascular permeability contributes to plasma leakage seen in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). An earlier study showed that senescent endothelial cells (ECs) altered the ECs permeability. Here we investigated the susceptibility of senescing human umbilical vein endothelial cells (HUVECs) to dengue virus infection and determined if dengue virus infection induces HUVECs senescence. Our results suggest that DENV type-2 (DENV-2) foci forming unit (FFU) and extracellular virus RNA copy number were reduced by at least 35% and 85% in infection of the intermediate young and early senescent HUVECs, respectively, in comparison to infection of young HUVECs. No to low infectivity was recovered from infection of late senescent HUVECs. DENV infection also increases the percentage of HUVECs expressing senescence-associated (SA)-β-gal, cells arrested at the G2/M phase or 4N DNA content stage and cells with enlarged morphology, indicative of senescing cells. Alteration of HUVECs morphology was recorded using impedance-based real-time cell analysis system following DENV-2 infection. These results suggest that senescing HUVECs do not support DENV infection and DENV infection induces HUVECs senescence. The finding highlights the possible role of induction of senescence in DENV infection of the endothelial cells.
    Matched MeSH terms: Cell Membrane Permeability/genetics
  2. Fulltext Bioavailability of Eurycomanone in Its Pure Form and in a Standardised Eurycoma longifolia Water Extract
    Ahmad N, Samiulla DS, Teh BP, Zainol M, Zolkifli NA, Muhammad A, et al.
    Pharmaceutics, 2018 Jul 11;10(3).
    PMID: 29997335 DOI: 10.3390/pharmaceutics10030090
    Eurycoma longifolia is one of the commonly consumed herbal preparations and its major chemical compound, eurycomanone, has been described to have antimalarial, antipyretic, aphrodisiac, and cytotoxic activities. Today, the consumption of E. longifolia is popular through the incorporation of its extract in food items, most frequently in drinks such as tea and coffee. In the current study, the characterisation of the physicochemical and pharmacokinetic (PK) attributes of eurycomanone were conducted via a series of in vitro and in vivo studies in rats and mice. The solubility and chemical stability of eurycomanone under the conditions of the gastrointestinal tract environment were determined. The permeability of eurycomanone was investigated by determining its distribution coefficient in aqueous and organic environments and its permeability using the parallel artificial membrane permeability assay system and Caco-2 cultured cells. Eurycomanone's stability in plasma and its protein-binding ability were measured by using an equilibrium dialysis method. Its stability in liver microsomes across species (mice, rat, dog, monkey, and human) and rat liver hepatocytes was also investigated. Along with the PK evaluations of eurycomanone in mice and rats, the PK parameters for the Malaysian Standard (MS: 2409:201) standardised water extract of E. longifolia were also evaluated in rats. Both rodent models showed that eurycomanone in both the compound form and extract form had a half-life of 0.30 h. The differences in the bioavailability of eurycomanone in the compound form between the rats (11.8%) and mice (54.9%) suggests that the PK parameters cannot be directly extrapolated to humans. The results also suggest that eurycomanone is not readily absorbed across biological membranes. However, once absorbed, the compound is not easily metabolised (is stable), hence retaining its bioactive properties, which may be responsible for the various reported biological activities.
    Matched MeSH terms: Cell Membrane Permeability
  3. Fulltext Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore
    Akimov SA, Volynsky PE, Galimzyanov TR, Kuzmin PI, Pavlov KV, Batishchev OV
    Sci Rep, 2017 09 22;7(1):12152.
    PMID: 28939906 DOI: 10.1038/s41598-017-12127-7
    Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.
    Matched MeSH terms: Cell Membrane Permeability
  4. Fulltext Pore formation in lipid membrane II: Energy landscape under external stress
    Akimov SA, Volynsky PE, Galimzyanov TR, Kuzmin PI, Pavlov KV, Batishchev OV
    Sci Rep, 2017 10 02;7(1):12509.
    PMID: 28970526 DOI: 10.1038/s41598-017-12749-x
    Lipid membranes are extremely stable envelopes allowing cells to survive in various environments and to maintain desired internal composition. Membrane permeation through formation of transversal pores requires substantial external stress. Practically, pores are usually formed by application of lateral tension or transmembrane voltage. Using the same approach as was used for obtaining continuous trajectory of pore formation in the stress-less membrane in the previous article, we now consider the process of pore formation under the external stress. The waiting time to pore formation proved a non-monotonous function of the lateral tension, dropping from infinity at zero tension to a minimum at the tension of several millinewtons per meter. Transmembrane voltage, on the contrary, caused the waiting time to decrease monotonously. Analysis of pore formation trajectories for several lipid species with different spontaneous curvatures and elastic moduli under various external conditions provided instrumental insights into the mechanisms underlying some experimentally observed phenomena.
    Matched MeSH terms: Cell Membrane Permeability
  5. Enhanced nanocurcumin toxicity against (PC3) tumor and microbial by using magnetic field in vitro
    Aldahoun MA, Jaafar MS, Al-Akhras MH, Bououdina M
    Artif Cells Nanomed Biotechnol, 2017 Jun;45(4):843-853.
    PMID: 27137748 DOI: 10.1080/21691401.2016.1178137
    Curcumin is more soluble in ethanol, dimethylsulfoxide, methanol and acetone than in water. In this study, nanocurcumin combined with 8 mT AC static magnetic field was used to enhance cellular uptake, bioavailability, and ultimate efficiency of curcumin against prostate cancer cell line (PC3), four bacteria strains (two Gram positive: Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 29213 and two Gram negative: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), mammalian cell line (HEK) and human erythrocytes (RBC). The efficiency (E%) between IC50 of nanocurcumin combined with magnetic field (NANOCUR-MF) and control against PC3 was 35.93%, which is three times higher compared to curcumin combined with magnetic field (CUR-MF); i.e., 10.77%. However, their E% against HEK was not significant; 1.4% for NANOCUR-MF and 1.95% for CUR-MF. Moreover, depending in minimum bacterial concentration (MBC), the use of MF leads to a reduction of MBCs for all tested bacteria compared with control. The obtained results established the applicability of (MF) in enhancing cellular uptake for PC3 and tested bacteria strains by increasing the penetration of drug (nanocurcumin and parent curcumin) into cell with fixing mild cytotoxic profile for HEK and RBC.
    Matched MeSH terms: Cell Membrane Permeability
  6. TRAIL-based tumor sensitizing galactoxyloglucan, a novel entity for targeting apoptotic machinery
    Aravind SR, Joseph MM, George SK, Dileep KV, Varghese S, Rose-James A, et al.
    Int J Biochem Cell Biol, 2015 Feb;59:153-66.
    PMID: 25541375 DOI: 10.1016/j.biocel.2014.11.019
    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for cancer therapy due to its ability to selectively induce apoptosis in cancer cells, without causing significant toxicity in normal tissues. We previously reported that galactoxyloglucan (PST001) possesses significant antitumor and immunomodulatory properties. However, the exact mechanism in mediating this anticancer effect is unknown. This study, for the first time, indicated that PST001 sensitizes non-small cell lung cancer (A549) and nasopharyngeal (KB) cells to TRAIL-mediated apoptosis. In vitro studies suggested that PST001 induced apoptosis primarily via death receptors and predominantly activated caspases belonging to the extrinsic apoptotic cascade. Microarray profiling of PST001 treated A549 and KB cells showed the suppression of survivin (BIRC5) and anti-apoptotic Bcl-2, as well as increased cytochrome C. TaqMan low density array analysis of A549 cells also confirmed that the induction of apoptosis by the polysaccharide occurred through the TRAIL-DR4/DR5 pathways. This was finally confirmed by in silico analysis, which revealed that PST001 binds to TRAIL-DR4/DR5 complexes more strongly than TNF and Fas ligand-receptor complexes. In summary, our results suggest the potential of PST001 to be developed as an anticancer agent that not only preserves innate biological activity of TRAIL, but also sensitizes cancer cells to TRAIL-mediated apoptosis.
    Matched MeSH terms: Cell Membrane Permeability/drug effects
  7. Dentatin isolated from Clausena excavata induces apoptosis in MCF-7 cells through the intrinsic pathway with involvement of NF-κB signalling and G0/G1 cell cycle arrest: a bioassay-guided approach
    Arbab IA, Abdul AB, Sukari MA, Abdullah R, Syam S, Kamalidehghan B, et al.
    J Ethnopharmacol, 2013 Jan 9;145(1):343-54.
    PMID: 23178663 DOI: 10.1016/j.jep.2012.11.020
    Clausena excavata Burm. f. has been used in folk medicines in eastern Thailand for the treatment of cancer.
    Matched MeSH terms: Cell Membrane Permeability/drug effects
  8. Fulltext Dentatin Induces Apoptosis in Prostate Cancer Cells via Bcl-2, Bcl-xL, Survivin Downregulation, Caspase-9, -3/7 Activation, and NF-κB Inhibition
    Arbab IA, Looi CY, Abdul AB, Cheah FK, Wong WF, Sukari MA, et al.
    Evid Based Complement Alternat Med, 2012;2012:856029.
    PMID: 23091559 DOI: 10.1155/2012/856029
    This study was set to investigate antiproliferative potential of dentatin (a natural coumarin isolated from Clausena excavata Burm. F) against prostate cancer and to delineate the underlying mechanism of action. Treatment with dentatin dose-dependently inhibited cell growth of PC-3 and LNCaP prostate cancer cell lines, whereas it showed less cytotoxic effects on normal prostate epithelial cell line (RWPE-1). The inhibitory effect of dentatin on prostate cancer cell growth was due to induction of apoptosis as evidenced by Annexin V staining and cell shrinkage. We found that dentatin-mediated accumulation of reactive oxygen species (ROS) and downregulated expression levels of antiapoptotic molecules (Bcl-2, Bcl-xL, and Survivin), leading to disruption of mitochondrial membrane potential (MMP), cell membrane permeability, and release of cytochrome c from the mitochondria into the cytosol. These effects were associated with induction of caspase-9, -3/7 activities, and subsequent DNA fragmentation. In addition, we found that dentatin inhibited TNF-α-induced nuclear translocation of p65, suggesting dentatin as a potential NF-κB inhibitor. Thus, we suggest that dentatin may have therapeutic value in prostate cancer treatment worthy of further development.
    Matched MeSH terms: Cell Membrane Permeability
  9. S-allylcysteine improves ischemia/reperfusion alteration on cardiac function, antioxidant, and mitochondrial permeability
    Aziz NF, Ramalingam A, Latip J, Zainalabidin S
    Life Sci, 2021 Mar 15;269:119080.
    PMID: 33465387 DOI: 10.1016/j.lfs.2021.119080
    S-Allylcysteine (SAC) is an extensively studied natural product which has been proven to confer cardioprotection. This potentiates SAC into many clinical relevance possibilities, hence, the use of it ought to be optimally elucidated. To further confirm this, an ischemia/reperfusion model has been used to determine SAC at 10 mM and 50 mM on cardiac function, cardiac marker, and mitochondrial permeability. Using Langendorff setup, 24 adult male Wistar rats' hearts were isolated to be perfused with Kreb-Henseleit buffer throughout the ischemia/reperfusion method. After 20 min of stabilization, global ischemia was induced by turning off the perfusion for 35 min followed by 60 min of reperfusion with either Kreb-Henseleit buffer or SAC with the dose of 10 mM or 50 mM. The cardiac function was assessed and coronary effluent was collected at different timepoints throughout the experiment for lactate dehydrogenase (LDH) measurement. The harvested hearts were then used to measure glutathione while isolated mitochondria for mPTP analysis. SAC-reperfused hearts were shown to prevent the aggravation of cardiac function after I/R induction. It also dose-dependently upregulated glutathione reductase and glutathione level and these were also accompanied by significant reduction of LDH leakage and preserved mitochondrial permeability. Altogether, SAC dose-dependently was able to recover the post-ischemic cardiac function deterioration alongside with improvement of glutathione metabolism and mitochondrial preservation. These findings highly suggest that SAC when sufficiently supplied to the heart would be able to prevent the deleterious complications after the ischemic insult.
    Matched MeSH terms: Cell Membrane Permeability/drug effects*
  10. In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages
    Chachuli SH, Nawaz A, Shah K, Naharudin I, Wong TW
    Pharm Res, 2016 06;33(6):1497-508.
    PMID: 26951565 DOI: 10.1007/s11095-016-1893-5
    PURPOSE: Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages.

    METHODS: Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques.

    RESULTS: The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary.

    CONCLUSION: Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.

    Matched MeSH terms: Cell Membrane Permeability*
  11. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate
    Charoo NA, Shamsher AA, Lian LY, Abrahamsson B, Cristofoletti R, Groot DW, et al.
    J Pharm Sci, 2014 Feb;103(2):378-91.
    PMID: 24382794 DOI: 10.1002/jps.23817
    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8.
    Matched MeSH terms: Cell Membrane Permeability
  12. Fulltext Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy
    Che Nordin MA, Teow SY
    Molecules, 2018 Feb 06;23(2).
    PMID: 29415435 DOI: 10.3390/molecules23020335
    The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases. Most therapeutic antibodies have been approved by Food and Drug Administration (FDA) mainly for targeting cancers. Previous studies have also demonstrated the promising effect of therapeutic antibodies against HIV-1, but there are several limitations in this therapy, particularly when the viral targets are intracellular proteins. The conventional antibodies do not cross the cell membrane, hence, the pathogenic intracellular proteins cannot be targeted with this classical therapeutic approach. Over the years, the advancement of antibody engineering has permitted the therapeutic antibodies to comprehensively target both extra- and intra-cellular proteins in various infections and diseases. This review aims to update on the current progress in the development of antibody-based treatment against intracellular targets in HIV-1 infection. We also attempt to highlight the challenges and limitations in the development of antibody-based therapeutic modalities against HIV-1.
    Matched MeSH terms: Cell Membrane Permeability*
  13. Purification of human adipose-derived stem cells from fat tissues using PLGA/silk screen hybrid membranes
    Chen DC, Chen LY, Ling QD, Wu MH, Wang CT, Suresh Kumar S, et al.
    Biomaterials, 2014 May;35(14):4278-87.
    PMID: 24565521 DOI: 10.1016/j.biomaterials.2014.02.004
    The purification of human adipose-derived stem cells (hADSCs) from human adipose tissue cells (stromal vascular fraction) was investigated using membrane filtration through poly(lactide-co-glycolic acid)/silk screen hybrid membranes. Membrane filtration methods are attractive in regenerative medicine because they reduce the time required to purify hADSCs (i.e., less than 30 min) compared with conventional culture methods, which require 5-12 days. hADSCs expressing the mesenchymal stem cell markers CD44, CD73, and CD90 were concentrated in the permeation solution from the hybrid membranes. Expression of the surface markers CD44, CD73, and CD99 on the cells in the permeation solution from the hybrid membranes, which were obtained using 18 mL of feed solution containing 50 × 10⁴ cells, was statistically significantly higher than that of the primary adipose tissue cells, indicating that the hADSCs can be purified in the permeation solution by the membrane filtration method. Cells expressing the stem cell-associated marker CD34 could be successfully isolated in the permeation solution, whereas CD34⁺ cells could not be purified by the conventional culture method. The hADSCs in the permeation solution demonstrated a superior capacity for osteogenic differentiation based on their alkali phosphatase activity, their osterix gene expression, and the results of mineralization analysis by Alizarin Red S and von Kossa staining compared with the cells from the suspension of human adipose tissue. These results suggest that the hADSCs capable of osteogenic differentiation preferentially permeate through the hybrid membranes.
    Matched MeSH terms: Cell Membrane Permeability/drug effects
  14. Intracellular antigen determination by flow cytometry in leukaemic cells
    Chin SF, Cheong SK
    Malays J Pathol, 1994 Jun;16(1):69-73.
    PMID: 16329579
    Several fixation and permeabilization techniques that enable the flow cytometric analysis of the cell contents have been introduced in recent years. These methods allow sensitive detection of intracellular antigens that facilitates the diagnosis of certain diseases. We have undertaken in this study to evaluate a simple method of fixation and permeabilization using 2% paraformaldehyde and Tween 20. Intracellular antigens in three different leukaemia cases were analysed. We found that the method was reliable and easy. Intracellular kappa light chains were found in abundance in a case of plasma cell leukaemia. CD3 and CD22 were found in greater amount intracellularly than on the surface in pre-T-ALL and pre-pre B-ALL respectively.
    Matched MeSH terms: Cell Membrane Permeability
  15. Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells
    Fong LY, Ng CT, Zakaria ZA, Baharuldin MT, Arifah AK, Hakim MN, et al.
    Phytother Res, 2015 Oct;29(10):1501-8.
    PMID: 26171791 DOI: 10.1002/ptr.5404
    The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-α), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-α in human aortic endothelial cells (HAEC). TNF-α caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)-dextran. Asiaticoside pretreatment significantly suppressed TNF-α-induced increased permeability. Asiaticoside also prevented TNF-α-induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF-α was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti-hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D-induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF-α without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F-actin organization.
    Matched MeSH terms: Cell Membrane Permeability
  16. Fulltext Cytotoxicity anticancer activities of anastrozole against breast, liver hepatocellular, and prostate cancer cells
    Hassan F, El-Hiti GA, Abd-Allateef M, Yousif E
    Saudi Med J, 2017 Apr;38(4):359-365.
    PMID: 28397941 DOI: 10.15537/smj.2017.4.17061
    OBJECTIVES: To investigate the cytotoxic effect of anastrozole on breast (MCF7), liver hepatocellular (HepG2), and prostate (PC3) cancer cells. Methods: This is a prospective study. Anastrozole's mechanism of apoptosis in living cells was also determined by high content screening (HCS) assay. Methylthiazol tetrazolium (MTT) assay was carried out at the Centre of Biotechnology Research's, Al-Nahrain University, Baghdad, Iraq between July 2015 and October 2015. The HCS assay was performed at the Centre for Natural Product Research  and Drug Discovery, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia between November 2015 and February 2016. Results: The most significant cytotoxic effect of anastrozole towards 3 cancer cell lines was obtained when its concentration was 400 µg/mL. The MCF7 cells were more sensitive to anastrozole compared with the HepG2 and PC-3 cells. There was a significant increase in membrane permeability, cytochrome c and nuclear intensity when anastrozole (200 µg/mL) was used compared with doxorubicin (20 µg/mL) as a standard. Also, there was a significant decrease in cell viability and mitochondrial membrane permeability when anastrozole (200 µg/mL) was used compared with positive control. Conclusion: Anastrozole showed cytotoxic effects against the MCF7, HepG2, and PC3 cell lines as determined in-vitro by the MTT assay. The HCS technique also showed toxic effect towards MCF7. It is evident that anastrozole inhibits the aromatase enzyme preventing the aromatization mechanism; however, it has a toxic effect.
    Matched MeSH terms: Cell Membrane Permeability/drug effects
  17. Fulltext In Vitro and In Vivo toxicity profiling of ammonium-based deep eutectic solvents
    Hayyan M, Looi CY, Hayyan A, Wong WF, Hashim MA
    PLoS One, 2015;10(2):e0117934.
    PMID: 25679975 DOI: 10.1371/journal.pone.0117934
    The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes.
    Matched MeSH terms: Cell Membrane Permeability/drug effects
  18. The effects of Naja sumatrana venom cytotoxin, sumaCTX on alteration of the secretome in MCF-7 breast cancer cells following membrane permeabilization
    Hiu JJ, Yap MKK
    Int J Biol Macromol, 2021 Aug 01;184:776-786.
    PMID: 34174307 DOI: 10.1016/j.ijbiomac.2021.06.145
    Naja sumatrana venom cytotoxin (sumaCTX) is a basic protein which belongs to three-finger toxin family. It has been shown to induce caspase-dependent, mitochondrial-mediated apoptosis in MCF-7 cells at lower concentrations. This study aimed to investigate the alteration of secretome in MCF-7 cells following membrane permeabilization by high concentrations of sumaCTX, using label-free quantitative (LFQ) approach. The degree of membrane permeabilization of sumaCTX was determined by lactate dehydrogenase (LDH) assay and calcein-propidium iodide (PI) assays. LDH and calcein-PI assays revealed time-dependent membrane permeabilization within a narrow concentration range. However, as toxin concentrations increased, prolonged exposure of MCF-7 cells to sumaCTX did not promote the progression of membrane permeabilization. The secretome analyses showed that membrane permeabilization was an event preceding the release of intracellular proteins. Bioinformatics analyses of the LFQ secretome revealed the presence of 105 significantly distinguished proteins involved in metabolism, structural supports, inflammatory responses, and necroptosis in MCF-7 cells treated with 29.8 μg/mL of sumaCTX. Necroptosis was presumably an initial stress response in MCF-7 cells when exposed to high sumaCTX concentration. Collectively, sumaCTX-induced the loss of membrane integrity in a concentration-dependent manner, whereby the cell death pattern of MCF-7 cells transformed from apoptosis to necroptosis with increasing toxin concentrations.
    Matched MeSH terms: Cell Membrane Permeability/drug effects
  19. Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery
    Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Nakamura Y, Chuang VTG, et al.
    J Control Release, 2018 05 10;277:23-34.
    PMID: 29530390 DOI: 10.1016/j.jconrel.2018.02.037
    Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA. Among the CPPs evaluated, a cyclic polypeptide composed of D-dodecaarginines, palmitoyl-cyclic-(D-Arg)12 was the most effective for facilitating the cellular uptake of HSA by HeLa cells. Such a superior cell-penetrating capability is primarily mediated by macropinocytosis. The effect of the CPP on pharmacological activity was examined using three drugs loaded in HSA via three different methods: a) an HSA-paclitaxel complex, b) an HSA-doxorubicin covalent conjugate and c) an HSA-thioredoxin fusion protein. The results showed that cell-penetrating efficiency was increased with a corresponding and significant enhancement in pharmacological activity. In conclusion, palmitoyl-cyclic-(D-Arg)12/HSA is a versatile cell-penetrating drug delivery system with great potential for use as a nano-carrier for a wide diversity of pharmaceutical applications.
    Matched MeSH terms: Cell Membrane Permeability/drug effects*; Cell Membrane Permeability/physiology
  20. A bismuth diethyldithiocarbamate compound promotes apoptosis in HepG2 carcinoma, cell cycle arrest and inhibits cell invasion through modulation of the NF-κB activation pathway
    Ishak DH, Ooi KK, Ang KP, Akim AM, Cheah YK, Nordin N, et al.
    J Inorg Biochem, 2014 Jan;130:38-51.
    PMID: 24176918 DOI: 10.1016/j.jinorgbio.2013.09.018
    The compound with R=CH2CH3 in Bi(S2CNR2)3 (1) is highly cytotoxic against a range of human carcinoma, whereas that with R=CH2CH2OH (2) is considerably less so. Both 1 and 2 induce apoptosis in HepG2 cells with some evidence for necrosis induced by 2. Based on DNA fragmentation, caspase activities and human apoptosis PCR-array analysis, both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. While both compounds activate mitochondrial and FAS apoptotic pathways, compound 1 was also found to induce another death receptor-dependent pathway by induction of CD40, CD40L and TNF-R1 (p55). Further, 1 highly expressed DAPK1, a tumour suppressor, with concomitant down-regulation of XIAP and NF-κB. Cell cycle arrest at the S and G2/M phases correlates with the inhibition of the growth of HepG2 cells. The cell invasion rate of 2 is 10-fold higher than that of 1, a finding correlated with the down-regulation of survivin and XIAP expression by 1. Compounds 1 and 2 interact with DNA through different binding motifs with 1 interacting with AT- or TA-specific sites followed by inhibition of restriction enzyme digestion; 2 did not interfere with any of the studied restriction enzymes.
    Matched MeSH terms: Cell Membrane Permeability/drug effects
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