Displaying publications 1 - 20 of 84 in total

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  1. Fulltext (R)-(+)-α-lipoic acid protected NG108-15 cells against H₂O₂-induced cell death through PI3K-Akt/GSK-3β pathway and suppression of NF-κβ-cytokines
    Kamarudin MN, Mohd Raflee NA, Hussein SS, Lo JY, Supriady H, Abdul Kadir H
    Drug Des Devel Ther, 2014;8:1765-80.
    PMID: 25336920 DOI: 10.2147/DDDT.S67980
    Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer's disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R)-(+)-alpha-lipoic acid (R-LA) against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours) significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5-50 μM) aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor) and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β) and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α). The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for the treatment of neurodegenerative diseases.
    Matched MeSH terms: Cell Death/drug effects
  2. Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)
    Er HM, Cheng EH, Radhakrishnan AK
    J Ethnopharmacol, 2007 Sep 25;113(3):448-56.
    PMID: 17698306
    The anti-proliferative effects of the aqueous and methanol extracts of leaves of Pereskia bleo (Kunth) DC (Cactaceae) against a mouse mammary cancer cell line (4T1) and a normal mouse fibroblast cell line (NIH/3T3) were evaluated under an optimal (in culture medium containing 10% foetal bovine serum (FBS)) and a sub-optimal (in culture medium containing 0.5% FBS) conditions. Under the optimal condition, the aqueous extract showed a significant (p<0.05) anti-proliferative effect at 200 microg/mL and 300 microg/mL in 4T1 cells and 300 microg/mL in NIH/3T3 cells, whereas the methanol extract did not show any notable anti-proliferative effect in these cell lines, at any of the concentrations tested. Under the sub-optimal condition, the aqueous extract showed a significant (p<0.05) anti-proliferative effect at 200 microg/mL and 300 microg/mL in NIH/3T3 cells, whilst the methanol extract showed a significant (p<0.05) anti-proliferative effect at 200 microg/mL and 300 microg/mL in both cell lines. An upward trend of apoptosis was observed in both 4T1 and NIH/3T3 cells treated with increasing concentrations of the aqueous extract. The level of apoptosis observed at all the concentrations of the aqueous extract tested was consistently higher than necrosis. There was a significant (p<0.05) increase in the level of necrosis observed in the 4T1 cells treated with 300 microg/mL of the methanol extract. Generally, the level of necrosis was noted to be higher than that of apoptosis in the methanol extract-treated cells. The mutagenicity assay performed showed that in the absence of S-9 liver metabolic activation, the extract was not mutagenic up to the concentration of 165 microg/mL . However, in the presence of S-9 liver metabolic activation, the aqueous extract was mutagenic at all the concentrations tested. This study shows that both the aqueous and methanol extracts of the leaves from Pereskia bleo (Kunth) DC (Cactaceae) do not have appreciable anti-proliferative effect on the 4T1 and NIH/3T3 cells as the EC(50) values obtained are greater than 50 microg/mL when tested under optimal culture condition. Moreover, the aqueous extract may form mutagenic compound(s) upon the metabolisation by liver enzymes.
    Matched MeSH terms: Cell Death/drug effects
  3. Antibacterial and cytotoxic effect of honey mediated copper nanoparticles synthesized using ultrasonic assistance
    Ismail NA, Shameli K, Wong MM, Teow SY, Chew J, Sukri SNAM
    Mater Sci Eng C Mater Biol Appl, 2019 Nov;104:109899.
    PMID: 31499959 DOI: 10.1016/j.msec.2019.109899
    In this study, a comparative study of effect using honey on copper nanoparticles (Cu-NPs) via simple, environmentally friendly process and inexpensive route was reported. Honey and ascorbic acid act as stabilizing and reducing agents with the assistance of sonochemical method. The products were characterized using UV-visible (UV-vis) spectroscopy, X-Ray Diffraction (XRD), High-Resolution Transmission Electron Microscopy (HRTEM), Field-Emission Scanning Electron Microscopy (FESEM) and Fourier Transform Infrared (FTIR) spectroscopy. The reddish brown colour demonstrated the formation of Cu-NPs and UV-visible proved the plasmon resonance of Cu-NPs. XRD also confirmed a highly pure Cu-NPs obtained with absence of copper oxide in which the structure is crystalline. The spherical size of the Cu-NPs was acquire in the presence of honey which is 3.68 ± 0.78 nm with narrow particle distribution. The antibacterial activity was seen against gram-positive and gram-negative bacteria which are Enterococcus faecalis (E. faecalis) and Escherichia coli (E. coli). At higher concentration of Cu-NPs, they were more effective in killing both bacteria. The Cu-NPs without and with honey exhibited toxicities toward normal and cancerous cells. However, Cu-NPs without honey showed more potent killing activity against normal and cancer cells.
    Matched MeSH terms: Cell Death/drug effects
  4. Antibacterial and wound healing analysis of gelatin/zeolite scaffolds
    Ninan N, Muthiah M, Bt Yahaya NA, Park IK, Elain A, Wong TW, et al.
    Colloids Surf B Biointerfaces, 2014 Mar 1;115:244-52.
    PMID: 24362063 DOI: 10.1016/j.colsurfb.2013.11.048
    In this article, gelatin/copper activated faujasites (CAF) composite scaffolds were fabricated by lyophilisation technique for promoting partial thickness wound healing. The optimised scaffold with 0.5% (w/w) of CAF, G (0.5%), demonstrated pore size in the range of 10-350 μm. Agar disc diffusion tests verified the antibacterial role of G (0.5%) and further supported that bacterial lysis was due to copper released from the core of CAF embedded in the gelatin matrix. The change in morphology of bacteria as a function of CAF content in gelatin scaffold was studied using SEM analysis. The confocal images revealed the increase in mortality rate of bacteria with increase in concentration of incorporated CAF in gelatin matrix. Proficient oxygen supply to needy cells is a continuing hurdle faced by tissue engineering scaffolds. The dissolved oxygen measurements revealed that CAF embedded in the scaffold were capable of increasing oxygen supply and thereby promote cell proliferation. Also, G (0.5%) exhibited highest cell viability on NIH 3T3 fibroblast cells which was mainly attributed to the highly porous architecture and its ability to enhance oxygen supply to cells. In vivo studies conducted on Sprague Dawley rats revealed the ability of G (0.5%) to promote skin regeneration in 20 days. Thus, the obtained data suggest that G (0.5%) is an ideal candidate for wound healing applications.
    Matched MeSH terms: Cell Death/drug effects
  5. Fulltext Anticancer Drug Discovery from Microbial Sources: The Unique Mangrove Streptomycetes
    Law JW, Law LN, Letchumanan V, Tan LT, Wong SH, Chan KG, et al.
    Molecules, 2020 Nov 17;25(22).
    PMID: 33212836 DOI: 10.3390/molecules25225365
    Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; however, there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals. This suggested the importance of the prompt detection, effective treatment, and prevention strategies. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites. Streptomycetes from mangrove environments attract researchers' attention due to their ability to synthesize diverse, interesting bioactive metabolites. The present review highlights research on mangrove-derived streptomycetes and the production of anticancer-related compounds from these microorganisms. Research studies conducted between 2008 and 2019, specifically mentioning the isolation of streptomycetes from mangrove areas and described the successful purification of compound(s) or generation of crude extracts with cytotoxic activity against human cancer cell lines, were compiled in this review. It is anticipated that there will be an increase in prospects for mangrove-derived streptomycetes as one of the natural resources for the isolation of chemotherapeutic agents.
    Matched MeSH terms: Cell Death/drug effects
  6. Fulltext Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro
    Yaacob NS, Hamzah N, Nik Mohamed Kamal NN, Zainal Abidin SA, Lai CS, Navaratnam V, et al.
    BMC Complement Altern Med, 2010;10:42.
    PMID: 20684795 DOI: 10.1186/1472-6882-10-42
    The leaves of Strobilanthes crispus (S. crispus) which is native to the regions of Madagascar to the Malay Archipelago, are used in folk medicine for their antidiabetic, diuretic, anticancer and blood pressure lowering properties. Crude extracts of this plant have been found to be cytotoxic to human cancer cell lines and protective against chemically-induced hepatocarcinogenesis in rats. In this study, the cytotoxicity of various sub-fractions of dichloromethane extract isolated from the leaves of S. crispus was determined and the anticancer activity of one of the bioactive sub-fractions, SC/D-F9, was further analysed in breast and prostate cancer cell lines.
    Matched MeSH terms: Cell Death/drug effects*
  7. Fulltext Antimycobacterial susceptibility evaluation of rifampicin and isoniazid benz-hydrazone in biodegradable polymeric nanoparticles against Mycobacterium tuberculosis H37Rv strain
    Hakkimane SS, Shenoy VP, Gaonkar SL, Bairy I, Guru BR
    Int J Nanomedicine, 2018;13:4303-4318.
    PMID: 30087562 DOI: 10.2147/IJN.S163925
    INTRODUCTION: Tuberculosis (TB) is the single largest infectious disease which requires a prolonged treatment regime with multiple drugs. The present treatment for TB includes frequent administration of a combination of four drugs for a duration of 6 months. This leads to patient's noncompliance, in addition to developing drug-resistant strains which makes treatment more difficult. The formulation of drugs with biodegradable polymeric nanoparticles (NPs) promises to overcome this problem.

    MATERIALS AND METHODS: In this study, we focus on two important drugs used for TB treatment - rifampicin (RIF) and isoniazid (INH) - and report a detailed study of RIF-loaded poly lactic-co-glycolic acid (PLGA) NPs and INH modified as INH benz-hydrazone (IH2) which gives the same therapeutic effect as INH but is more stable and enhances the drug loading in PLGA NPs by 15-fold compared to INH. The optimized formulation was characterized using particle size analyzer, scanning electron microscopy and transmission electron microscopy. The drug release from NPs and stability of drug were tested in different pH conditions.

    RESULTS: It was found that RIF and IH2 loaded in NPs release in a slow and sustained manner over a period of 1 month and they are more stable in NPs formulation compared to the free form. RIF- and IH2-loaded NPs were tested for antimicrobial susceptibility against Mycobacterium tuberculosis H37Rv strain. RIF loaded in PLGA NPs consistently inhibited the growth at 70% of the minimum inhibitory concentration (MIC) of pure RIF (MIC level 1 µg/mL), and pure IH2 and IH2-loaded NPs showed inhibition at MIC equivalent to the MIC of INH (0.1 µg/mL).

    CONCLUSION: These results show that NP formulations will improve the efficacy of drug delivery for TB treatment.

    Matched MeSH terms: Cell Death/drug effects
  8. Fulltext Antioxidants, phytochemicals, and cytotoxicity studies on Phaleria macrocarpa (Scheff.) Boerl seeds
    Lay MM, Karsani SA, Banisalam B, Mohajer S, Abd Malek SN
    Biomed Res Int, 2014;2014:410184.
    PMID: 24818141 DOI: 10.1155/2014/410184
    In recent years, the utilization of certain medicinal plants as therapeutic agents has drastically increased. Phaleria macrocarpa (Scheff.) Boerl is frequently used in traditional medicine. The present investigation was undertaken with the purpose of developing pharmacopoeial standards for this species. Nutritional values such as ash, fiber, protein, fat, and carbohydrate contents were investigated, and phytochemical screenings with different reagents showed the presence of flavonoids, glycosides, saponin glycosides, phenolic compounds, steroids, tannins, and terpenoids. Our results also revealed that the water fraction had the highest antioxidant activity compared to the methanol extract and other fractions. The methanol and the fractionated extracts (hexane, chloroform, ethyl acetate, and water) of P. macrocarpa seeds were also investigated for their cytotoxic effects on selected human cancer cells lines (MCF-7, HT-29, MDA-MB231, Ca Ski, and SKOV-3) and a normal human fibroblast lung cell line (MRC-5). Information from this study can be applied for future pharmacological and therapeutic evaluations of the species, and may assist in the standardization for quality, purity, and sample identification. To the best of our knowledge, this is the first report on the phytochemical screening and cytotoxic effect of the crude and fractionated extracts of P. macrocarpa seeds on selected cells lines.
    Matched MeSH terms: Cell Death/drug effects
  9. Arabinoxylan/graphene-oxide/nHAp-NPs/PVA bionano composite scaffolds for fractured bone healing
    Aslam Khan MU, Haider A, Abd Razak SI, Abdul Kadir MR, Haider S, Shah SA, et al.
    J Tissue Eng Regen Med, 2021 04;15(4):322-335.
    PMID: 33432773 DOI: 10.1002/term.3168
    The importance of bone scaffolds has increased many folds in the last few years; however, during bone implantation, bacterial infections compromise the implantation and tissue regeneration. This work is focused on this issue while not compromising on the properties of a scaffold for bone regeneration. Biocomposite scaffolds (BS) were fabricated via the freeze-drying technique. The samples were characterized for structural changes, surface morphology, porosity, and mechanical properties through spectroscopic (Fourier transform-infrared [FT-IR]), microscopic (scanning electron microscope [SEM]), X-ray (powder X-ray diffraction and energy-dispersive X-ray), and other analytical (Brunauer-Emmett-Teller, universal testing machine Instron) techniques. Antibacterial, cellular, and hemocompatibility assays were performed using standard protocols. FT-IR confirmed the interactions of all the components. SEM illustrated porous and interconnected porous morphology. The percentage porosity was in the range of 49.75%-67.28%, and the pore size was 215.65-470.87 µm. The pore size was perfect for cellular penetration. Thus, cells showed significant proliferation onto these scaffolds. X-ray studies confirmed the presence of nanohydroxyapatite and graphene oxide (GO). The cell viability was 85%-98% (BS1-BS3), which shows no significant toxicity of the biocomposite. Furthermore, the biocomposites exhibited better antibacterial activity, no effect on the blood clotting (normal in vitro blood clotting), and less than 5% hemolysis. The ultimate compression strength for the biocomposites increased from 4.05 to 7.94 with an increase in the GO content. These exciting results revealed that this material has the potential for possible application in bone tissue engineering.
    Matched MeSH terms: Cell Death/drug effects
  10. Fulltext Arctium lappa L. root extract induces cell death via mitochondrial-mediated caspase-dependent apoptosis in Jurkat human leukemic T cells
    Gurunanselage Don RAS, Yap MKK
    Biomed Pharmacother, 2019 Feb;110:918-929.
    PMID: 30572196 DOI: 10.1016/j.biopha.2018.12.023
    Arctium lappa L. is a perennial herb traditionally consumed to improve well-being. It has been widely reported for its antioxidant properties; however, very little is known for its exact mechanisms underlying the anticancer activity. This study aimed to investigate the mechanisms of anticancer action for different A. lappa root extracts. Arctium lappa root was extracted with ethanol, hexane and ethyl acetate, then examined for in vitro anticancer activity against cancerous HeLa, MCF-7, Jurkat cell lines and non-cancerous 3T3 cell lines. Induction of apoptosis was determined by cellular morphological changes, mitochondrial membrane potential (ΔΨm), caspase-3/7 activity and DNA fragmentation. The active compounds present in the most potent root extracts were identified by LC-ESI-MS. Among all the extracts, ethyl acetate root extract has the highest potency with IC50 of 102.2 ± 42.4 μg/ml, followed by ethanolic root extract in Jurkat T cells, at 24 h. None of the extracts were cytotoxic against 3T3 cells, suggesting that the extracts were selective against cancerous cells only. Both ethyl acetate and ethanolic root extracts exhibited significant morphological changes in Jurkat T cells, including the detachment from adjacent cells, appearance of apoptotic bodies and cells shrinkage. The extracts treated cells also displayed an increase in caspase-3/7 activity and alteration in mitochondrial membrane potential. Only ethyl acetate root extract at IC50 induced DNA fragmentation in Jurkat T cells. LC-ESI-MS analysis of the extract revealed the presence of 8 compounds, of which only 6 compounds with various biological activities reported. These findings suggest that the ethyl acetate extract of A. lappa had strong anticancer potential and induced intrinsic apoptosis via loss of ΔΨm and activation of caspase-3/7 This study can provide new insight to the discovery of new promising lead compound in chemopreventive and chemotherapeutic strategies.
    Matched MeSH terms: Cell Death/drug effects
  11. Fulltext Autophagic cell death is induced by acetone and ethyl acetate extracts from Eupatorium odoratum in vitro: effects on MCF-7 and vero cell lines
    Harun FB, Syed Sahil Jamalullail SM, Yin KB, Othman Z, Tilwari A, Balaram P
    ScientificWorldJournal, 2012;2012:439479.
    PMID: 22666123 DOI: 10.1100/2012/439479
    Eupatorium odoratum (EO) contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action of EO extracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 μg/mL. These results thus suggest that acetone and ethyl acetate extracts of EO induce cell death through induction of autophagy and hold potential for development as potential anticancer drugs.
    Matched MeSH terms: Cell Death/drug effects*
  12. Bactericidal and cytotoxic activity of a diarylheptanoid (etlingerin) isolated from a ginger (Etlingera pubescens) endemic to Borneo
    Daniel-Jambun D, Ong KS, Lim YY, Tan JBL, Yap SW, Lee SM
    J Appl Microbiol, 2019 Jul;127(1):59-67.
    PMID: 31006174 DOI: 10.1111/jam.14287
    AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound.

    METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin.

    CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed.

    SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.

    Matched MeSH terms: Cell Death/drug effects
  13. Fulltext Bioactivities of Lyngbyabellins from Cyanobacteria of Moorea and Okeania Genera
    Fathoni I, Petitbois JG, Alarif WM, Abdel-Lateff A, Al-Lihaibi SS, Yoshimura E, et al.
    Molecules, 2020 Sep 01;25(17).
    PMID: 32882989 DOI: 10.3390/molecules25173986
    Cyanobacteria are reported as rich sources of secondary metabolites that provide biological activities such as enzyme inhibition and cytotoxicity. Ten depsipeptide derivatives (lyngbyabellins) were isolated from a Malaysian Moorea bouillonii and a Red Sea Okeania sp.: lyngbyabellins G (1), O (2), P (3), H (4), A (7), 27-deoxylyngbyabellin A (5), and homohydroxydolabellin (6). This study indicated that lyngbyabellins displayed cytotoxicity, antimalarial, and antifouling activities. The isolated compounds were tested for cytotoxic effect against human breast cancer cells (MCF7), for antifouling activity against Amphibalanus amphitrite barnacle larvae, and for antiplasmodial effect towards Plasmodium falciparum. Lyngbyabellins A and G displayed potent antiplasmodial effect against Plasmodium, whereas homohydroxydolabellin showed moderate effect. For antifouling activity, the side chain decreases the activity slightly, but the essential feature is the acyclic structure. As previously reported, the acyclic lyngbyabellins are less cytotoxic than the corresponding cyclic ones, and the side chain increases cytotoxicity. This study revealed that lyngbyabellins, despite being cytotoxic agents as previously reported, also exhibit antimalarial and antifouling activities. The unique chemical structures and functionalities of lyngbyabellin play an essential role in their biological activities.
    Matched MeSH terms: Cell Death/drug effects
  14. Carbonate apatite nanoparticles carry siRNA(s) targeting growth factor receptor genes egfr1 and erbb2 to regress mouse breast tumor
    Tiash S, Kamaruzman NIB, Chowdhury EH
    Drug Deliv, 2017 Nov;24(1):1721-1730.
    PMID: 29119846 DOI: 10.1080/10717544.2017.1396385
    Cancer cells lose their control on cell cycle by numerous genetic and epigenetic alterations. In a tumor, these cells highly express growth factor receptors (GFRs), eliciting growth, and cell division. Among the GFRs, epidermal growth factor receptor-1 (EGFR1) (Her1/ERBB1) and epidermal growth factor receptor-2 (EGFR2) (Her2/ERBB2) from epidermal growth factor (EGF) family and insulin-like growth factor-1 receptor (IGF1R) are highly expressed on breast cancer cells, thus contributing to the aggressive growth and invasiveness, have been focused in this study. Moreover, overexpression of these receptors is related to suppression of cell death and conferring resistance against the classical drugs used to treat cancer nowadays. Therefore, silencing of these GFRs-encoding genes by using selective small interfering RNAs (siRNAs) could be a powerful approach to treat breast cancer. The inorganic pH sensitive carbonate apatite nanoparticles (NPs) were used as a nano-carrier to deliver siRNA(s) against single or multiple GFR genes in breast cancer cells as well as in a mouse model of breast carcinoma. Silencing of egfr1 and erbb2 simultaneously led to a reduction in cell viability with an increase in cell death signal in the cancer cells and regression of tumor growth in vivo.
    Matched MeSH terms: Cell Death/drug effects
  15. Cell death induced by hydroxyapatite on L929 fibroblast cells
    Inayat-Hussain SH, Rajab NF, Roslie H, Hussin AA, Ali AM, Annuar BO
    Med J Malaysia, 2004 May;59 Suppl B:176-7.
    PMID: 15468875
    Biomaterials intended for end-use application as bone-graft substitutes have to undergo safety evaluation. In this study, we investigated the in vitro cytotoxic effects especially to determine the mode of death of two hydroxyapatite compounds (HA2, HA3) which were synthesized locally. The methods used for cytotoxicity was the standard MTT assay whereas AO/PI staining was performed to determine the mode of cell death in HA treated L929 fibroblasts. Our results demonstrated that both HA2 and HA3 were not significantly cytotoxic as more than 75% cells after 72 hours treatment were viable. Furthermore, we found that the major mode of cell death in HA treated cells was apoptosis. In conclusion, our results demonstrated that these hydroxyapatite compounds are not cytotoxic where the mode of death was primarily via apoptosis.
    Matched MeSH terms: Cell Death/drug effects*
  16. Fulltext Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3) cells
    Hasan S, Al Ali H, Al-Qubaisi M, Zobir Hussein M, Ismail M, Zainal Z, et al.
    Int J Nanomedicine, 2012;7:3351-63.
    PMID: 22848164 DOI: 10.2147/IJN.S30809
    A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC₅₀ for CETN and ZLH are 617 and 670 μg/mL, respectively.
    Matched MeSH terms: Cell Death/drug effects
  17. Cytolytic effects and apoptosis induction of Newcastle disease virus strain AF2240 on anaplastic astrocytoma brain tumor cell line
    Ali R, Alabsi AM, Ali AM, Ideris A, Omar AR, Yusoff K, et al.
    Neurochem Res, 2011 Nov;36(11):2051-62.
    PMID: 21671106 DOI: 10.1007/s11064-011-0529-8
    Newcastle disease virus (NDV) is a member of genus Avulavirus within the family Paramyxoviridae. Interest of using NDV as an anticancer agent has arisen from its ability to kill tumor cells with limited toxicity to normal cells. In this investigation, the cytotolytic properties of NDV strain AF2240 were evaluated on brain tumor cell line, anaplastic astrocytoma (U-87MG), by using MTT assay. Cytological observations were studied using fluorescence microscopy and transmission electron microscopy to show the apoptogenic features of NDV on U-87MG. DNA laddering in agarose gel electrophoresis and terminal deoxyribonucleotide transferase-mediated dUTP-X nick end-labeling staining assay confirmed that the mode of cell death was by apoptosis. However, analysis of the cellular DNA content by flowcytometery showed that there was a loss of treated U-87MG cells in all cell cycle phases (G1, S and G2/M) accompanied with increasing in sub-G1 region (apoptosis peak). Early apoptosis was observed 6 h post-inoculation by annexin-V flow-cytometry method. It could be concluded that NDV strain AF2240 is a potent antitumor agent that induce apoptosis and its cytotoxicity increasing while increasing of time and virus titer.
    Matched MeSH terms: Cell Death/drug effects
  18. Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells
    Rati Selvaraju T, Khaza'ai H, Vidyadaran S, Sokhini Abd Mutalib M, Ramachandran V, Hamdan Y
    Int J Vitam Nutr Res, 2014;84(3-4):140-51.
    PMID: 26098478 DOI: 10.1024/0300-9831/a000201
    Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100-300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76% and 79% in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2%, 95.0%, and 95.6%, respectively (p<0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.
    Matched MeSH terms: Cell Death/drug effects*
  19. Fulltext Cytoprotective and Cytotoxic Effects of Rice Bran Extracts in Rat H9c2(2-1) Cardiomyocytes
    Tan XW, Bhave M, Fong AY, Matsuura E, Kobayashi K, Shen LH, et al.
    Oxid Med Cell Longev, 2016;2016:6943053.
    PMID: 27239253 DOI: 10.1155/2016/6943053
    This study was aimed at preliminarily assessing the cytoprotective and antioxidative effects of rice bran extracts (RBEs) from a Sarawak local rice variety (local name: "BJLN") and a commercial rice variety, "MR219," on oxidative stress in rat H9c2(2-1) cardiomyocytes. The cardiomyocytes were incubated with different concentrations of RBE and hydrogen peroxide (H2O2), respectively, to identify their respective IC50 values and safe dose ranges. Two nonlethal and close-to-IC50 doses of RBE were selected to evaluate their respective effects on H2O2 induced oxidative stress in cardiomyocytes. Both RBEs showed dose-dependent cytotoxicity effects on cardiomyocytes. H2O2 induction of cardiomyocytes pretreated with RBE further revealed the dose-dependent cytoprotective and antioxidative effects of RBE via an increase in IC50 values of H2O2. Preliminary analyses of induction effects of RBE and H2O2 on cellular antioxidant enzyme, catalase (CAT), also revealed their potential in regulating these activities and expression profile of related gene on oxidative stress in cardiomyocytes. Pretreated cardiomyocytes significantly upregulated the enzymatic activity and expression level of CAT under the exposure of H2O2 induced oxidative stress. This preliminary study has demonstrated the potential antioxidant effects of RBE in alleviating H2O2-mediated oxidative injuries via upregulation in enzymatic activities and expression levels of CAT.
    Matched MeSH terms: Cell Death/drug effects
  20. Cytotoxic benzophenone and triterpene from Garcinia hombroniana
    Jamila N, Khairuddean M, Yaacob NS, Kamal NN, Osman H, Khan SN, et al.
    Bioorg Chem, 2014 Jun;54:60-7.
    PMID: 24813683 DOI: 10.1016/j.bioorg.2014.04.003
    Garcinia hombroniana (seashore mangosteen) in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to investigate the bioactive chemical constituents of the bark of G. hombroniana. Ethyl acetate and dichloromethane extracts of G. hombroniana yielded two new (1, 9) and thirteen known compounds which were characterized by the spectral techniques of NMR, UV, IR and EI/ESI-MS, and identified as; 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone(1), 2,3',4,4'-tetrahydroxy-6-methoxybenzophenone (2), 2,3',4,6-tetrahydroxybenzophenone (3), 1,3,6,7-tetrahydroxyxanthone (4), 3,3',4',5,7-pentahydroxyflavone (5),3,3',5,5',7-pentahydroxyflavanone (6), 3,3',4',5,5',7-hexahydroxyflavone (7), 4',5,7-trihydroxyflavanone-7-rutinoside (8), 18(13→17)-abeo-3β-acetoxy-9α,13β-lanost-24E-en-26-oic acid (9), garcihombronane B (10), garcihombronane D (11), friedelan-3-one (12), lupeol (13), stigmasterol (14) and stigmasterol glucoside (15). In the in vitro cytotoxicity against MCF-7, DBTRG, U2OS and PC-3 cell lines, compounds 1 and 9 displayed good cytotoxic effects against DBTRG cancer cell lines. Compounds 1-8 were also found to possess significant antioxidant activities. Owing to these properties, this study can be further extended to explore more significant bioactive components of this plant.
    Matched MeSH terms: Cell Death/drug effects
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