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  1. Ismail S, Jalilian FA, Talebpour AH, Zargar M, Shameli K, Sekawi Z, et al.
    Biomed Res Int, 2013;2013:696835.
    PMID: 23484141 DOI: 10.1155/2013/696835
    Allium hirtifolium Boiss. known as Persian shallot, is a spice used as a traditional medicine in Iran and, Mediterranean region. In this study, the chemical composition of the hydromethanolic extract of this plant was analyzed using GC/MS. The result showed that 9-hexadecenoic acid, 11,14-eicosadienoic acid, and n-hexadecanoic acid are the main constituents. The antibacterial activity of the shallot extract was also examined by disk diffusion and microdilution broth assays. It was demonstrated that Persian shallot hydromethanolic extract was effective against 10 different species of pathogenic bacteria including methicillin resistant Staphylococcus aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Escherichia coli, Escherichia coli O157:H7, Salmonella typhimurium, Proteus mirabilis, and Klebsiella pneumoniae. Specifically, the minimum concentration of the extract which inhibited bacterial growth (MIC values) was 1.88 mg/mL for most of the gram-positive bacteria. This concentration was not much different from the concentration that was safe for mammalian cells (1.50 mg/mL) suggesting that the hydromethanolic extract of Persian shallot may be a safe and strong antibacterial agent.
    Matched MeSH terms: Cytotoxins/pharmacology*
  2. Chuah LO, Foo HL, Loh TC, Mohammed Alitheen NB, Yeap SK, Abdul Mutalib NE, et al.
    BMC Complement Altern Med, 2019 Jun 03;19(1):114.
    PMID: 31159791 DOI: 10.1186/s12906-019-2528-2
    BACKGROUND: Lactobacillus plantarum, a major species of Lactic Acid Bacteria (LAB), are capable of producing postbiotic metabolites (PM) with prominent probiotic effects that have been documented extensively for rats, poultry and pigs. Despite the emerging evidence of anticancer properties of LAB, very limited information is available on cytotoxic and antiproliferative activity of PM produced by L. plantarum. Therefore, the cytotoxicity of PM produced by six strains of L. plantarum on various cancer and normal cells are yet to be evaluated.

    METHODS: Postbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses.

    RESULTS: UL4 PM exhibited the lowest IC50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis.

    CONCLUSION: In conclusion, PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer.

    Matched MeSH terms: Cytotoxins/pharmacology
  3. D'Souza UJ, Zain A, Raju S
    Mutat Res, 2005 Mar 7;581(1-2):187-90.
    PMID: 15725618
    The genotoxic effect of the herbicide paraquat was studied in rat bone-marrow by means of the micronucleus assay. Paraquat at dose levels of 6, 15 and 30 mg/kg body weight was given to rats in a single application via the dermal route. Marrow was collected at 24, 48 and 72 h after the application. The micronucleus assay was done as recommended by standard procedures. Paraquat gave rise to an increase in the number of micronuclei in a dose-dependent manner. The number of micronucleated polychromatic erythrocytes showed a maximum at 48 h and the toxicity was further prolonged, as there was no complete recovery at 72 h. These findings suggest a genotoxic effect of paraquat even after exposure via dermal application.
    Matched MeSH terms: Cytotoxins/pharmacology*
  4. Kam WJ, Abas F, Hussain N, Mirhosseini H
    Nat Prod Res, 2020 Jul;34(13):1937-1941.
    PMID: 30691284 DOI: 10.1080/14786419.2018.1564296
    The objective of this study was to compare the antioxidant activity and cytotoxicity of Durio zibethinus M. (Durian) leaf extract from two extraction methods. Ultrasound-assisted extraction and Accelerated-solvent extraction were used to produce crude extract. The results revealed that UAE achieved 3× higher in total phenolic content in the leaf extract compared to ASE. DPPH radical scavenging activity was 4.6× higher in leaf extract from ASE. No significant differences reported in ferric reducing power, and total flavonoid content of the leaf extract between the two methods. Cytotoxicity via MTT assay demonstrated no significant differences in cell viability upon exposure to the leaf extract from both methods. This suggested that they were appropriate in producing Durio zibethinus M. leaf extract for end use application in food related product. Both ensured similar level of safety in Durio zibethinus M. leaf extract as a new potential ingredient for the food industry.
    Matched MeSH terms: Cytotoxins/pharmacology
  5. Mohideen M, Zulkepli S, Nik-Salleh NS, Zulkefeli M, Weber JF, Weber JF, et al.
    Arch Pharm Res, 2013 Jul;36(7):812-31.
    PMID: 23543632 DOI: 10.1007/s12272-013-0099-1
    A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from commercially available (3,4-dihydro-2H-pyran-2-yl)methanol/5-(hydroxymethyl)dihydrofuran-2(3H)-one in three steps with good to moderate overall yields and their cytotoxicity against lymphoblastic leukemic T cell line (Jurkat E6.1) have been evaluated. Among the synthesized analogs, (Z)-Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 μM). Structure-activity relationship study indicates that introducing substituent in phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the ring size of lactones (from six to five member) do not increase the cytotoxicity.
    Matched MeSH terms: Cytotoxins/pharmacology*
  6. Najim N, Bathich Y, Zain MM, Hamzah AS, Shaameri Z
    Molecules, 2010 Dec 17;15(12):9340-53.
    PMID: 21169884 DOI: 10.3390/molecules15129340
    The aim of this study was to investigate the in vitro cellular activity of novel spiroisoxazoline type compounds against normal and cancer cell lines from lung tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y), human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). Our bioassay program revealed that the spiroisoxazoline type compounds show cytotoxicity only in lymphoma cell lines, which is in contrast with the pyrrolidine precursor of these spiroisoxazoline compounds, where significant cytotoxicity is seen in all normal and cancer cell lines. These data suggest a tumour-specific mechanism of action. In addition these data also show that spiroisoxazoline compounds are non-toxic in the human neuronphenotypic neuroblastoma SH-SY5Y cell line, and furthermore that they might protect cells from neurodegenerative disease.
    Matched MeSH terms: Cytotoxins/pharmacology
  7. Malik FZ, Allaudin ZN, Loh HS, Nee TK, Hani H, Abdullah R
    BMC Complement Altern Med, 2016 May 23;16:139.
    PMID: 27216794 DOI: 10.1186/s12906-016-1120-2
    Duabanga grandiflora or known in Malaysia as Berembang Bukit, Megawasih, or Pedada Bukit, is a native plant of the Southeast Asian countries. In this study, the anti-viral properties of D. grandiflora were investigated.
    Matched MeSH terms: Cytotoxins/pharmacology
  8. Mohd Sakeh N, Md Razip NN, Mohd Ma'in FI, Abdul Bahari MN, Latif N, Akhtar MN, et al.
    Molecules, 2020 Jul 28;25(15).
    PMID: 32731323 DOI: 10.3390/molecules25153403
    Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
    Matched MeSH terms: Cytotoxins/pharmacology*
  9. 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: Cytotoxins/pharmacology*
  10. Saleem H, Htar TT, Naidu R, Zengin G, Ahmad I, Ahemad N
    Nat Prod Res, 2020 Sep;34(18):2602-2606.
    PMID: 30600720 DOI: 10.1080/14786419.2018.1543684
    In this study, phytochemical composition, antioxidant, enzyme inhibition and cytotoxic activities of methanol and dichloromethane (DCM) extracts of Bougainvillea glabra (B. glabra) flowers were investigated. Methanol extract was found to have higher total bioactive contents and UHPLC-MS analysis of methanol extract revealed the presence of well-known phenolic and flavonoid compounds. Antioxidant activities were performed by radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum (TAC) and metal chelating assays. From our result, we observed that methanol extract had many antioxidant compounds. The DCM extract exhibited higher cholinesterases and α-glucosidase enzyme inhibition, while methanol extract showed significant urease inhibition. Both extracts exhibited strong to moderate cytotoxicity against MCF-7, MDA-MB-231, CaSki, DU-145 and SW-480 cancer cells with IC50 values ranging from 88.49 to 304.7 µg/mL. The findings showed the B. glabra to possess considerable antioxidant, enzyme inhibition and cytotoxic potentials and therefore has potential to discover novel bioactive molecules.
    Matched MeSH terms: Cytotoxins/pharmacology
  11. Alshaibani M, Zin NM, Jalil J, Sidik N, Ahmad SJ, Kamal N, et al.
    J Microbiol Biotechnol, 2017 07 28;27(7):1249-1256.
    PMID: 28535606 DOI: 10.4014/jmb.1608.08032
    In our search for new sources of bioactive secondary metabolites from Streptomyces sp., the ethyl acetate extracts from endophytic Streptomyces SUK 25 afforded five active diketopiperazine (DKP) compounds. The aim of this study was to characterize the bioactive compounds isolated from endophytic Streptomyces SUK 25 and evaluate their bioactivity against multiple drug resistance (MDR) bacteria such as Enterococcus raffinosus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter spp., and their cytotoxic activities against the human hepatoma (HepaRG) cell line. The production of secondary metabolites by this strain was optimized through Thornton's medium. Isolation, purification, and identification of the bioactive compounds were carried out using high-performance liquid chromatography, high-resolution mass liquid chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance, and cryopreserved HepaRG cells were selected to test the cytotoxicity. The results showed that endophytic Streptomyces SUK 25 produces four active DKP compounds and an acetamide derivative, which were elucidated as cyclo-(L-Val-L-Pro), cyclo-(L-Leu-L-Pro), cyclo-(L-Phe-L-Pro), cyclo-(L-Val-L-Phe), and N-(7-hydroxy-6-methyl-octyl)-acetamide. These active compounds exhibited activity against methicillin-resistant S. aureus ATCC 43300 and Enterococcus raffinosus, with low toxicity against human hepatoma HepaRG cells. Endophytic Streptomyces SUK 25 has the ability to produce DKP derivatives biologically active against some MDR bacteria with relatively low toxicity against HepaRG cells line.
    Matched MeSH terms: Cytotoxins/pharmacology*
  12. Ibrahim MD, Kntayya SB, Mohd Ain N, Iori R, Ioannides C, Abdull Razis AF
    Molecules, 2018 Nov 27;23(12).
    PMID: 30486382 DOI: 10.3390/molecules23123092
    Glucoraphasatin (GRH), a glucosinolate present abundantly in the plants of the Brassicaceae family, is hydrolyzed by myrosinase to raphasatin, which is considered responsible for its cancer chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aims of this study are to determine the cytotoxicity of raphasatin, and to evaluate its potential to cause apoptosis and modulate cell cycle arrest in human breast adenocarcinoma MCF-7 cells. The cytotoxicity was determined following incubation of the cells with glucoraphasatin or raphasatin (0⁻100 µM), for 24, 48, and 72 h. GRH displayed no cytotoxicity as exemplified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. When myrosinase was added to the incubation system to convert GRH to raphasatin, cytotoxicity was evident. Exposure of the cells to raphasatin stimulated apoptosis, as was exemplified by cell shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation. Moreover, using Annexin V-FITC assay, raphasatin induced apoptosis, as witnessed by changes in cellular distribution of cells, at different stages of apoptosis; in addition, raphasatin caused the arrest of the MCF-7 cells at the G₂ + M phase. In conclusion, raphasatin demonstrated cancer chemopreventive potential against human breast adenocarcinoma (MCF-7) cells, through induction of apoptosis and cell cycle arrest.
    Matched MeSH terms: Cytotoxins/pharmacology*
  13. Vafaei A, Bin Mohamad J, Karimi E
    Nat Prod Res, 2019 Sep;33(17):2531-2535.
    PMID: 29527930 DOI: 10.1080/14786419.2018.1448810
    In this study the antioxidant and cytotoxicity activity of the Adonidia merrillii fruits were investigated using different solvent polarities (methanol, ethyl acetate and water). The results showed that the total phenolic and flavonoid contents of the methanolic extract was higher compare with other extract with respective values of 17.80 ± 0.45 mg gallic acid equivalents/g dry weight (DW) and 5.43 ± 0.33 mg rutin equivalents/g DW. Beside that The RP-HPLC analyses indicated the presence of gallic acid, pyrogallol, caffeic acid, vanillic acid, syringic acid, naringin and rutin. In the DPPH, NO2 and ABTS scavenging assays, the methanolic extract exhibited higher antioxidant activity as compared to the ethyl acetate and water extracts. The extracts exhibited moderate to weak cytotoxic activity in the assays using human hepatocytes (Chang liver cells) and NIH/3T3 (fibroblasts cell) cell lines. The findings showed the Adonidia merrillii fruit extracts to possess considerable antioxidant and cytotoxicity properties. The fruit, therefore, is a potential candidate for further work to discover antioxidant and cytotoxic drugs from natural sources.
    Matched MeSH terms: Cytotoxins/pharmacology
  14. Ling LT, Radhakrishnan AK, Subramaniam T, Cheng HM, Palanisamy UD
    Molecules, 2010 Apr;15(4):2139-51.
    PMID: 20428033 DOI: 10.3390/molecules15042139
    Thirteen Malaysian plants; Artocarpus champeden, Azadirachta indica, Fragaria x ananassa, Garcinia mangostana, Lawsonia inermis, Mangifera indica, Nephelium lappaceum, Nephelium mutobile, Peltophorum pterocarpum, Psidium guajava and Syzygium aqueum, selected for their use in traditional medicine, were subjected to a variety of assays. Antioxidant capability, total phenolic content, elemental composition, as well as it cytotoxity to several cell lines of the aqueous and ethanolic extracts from different parts of these selected Malaysian plants were determined. In general, the ethanolic extracts were better free radical scavengers than the aqueous extracts and some of the tested extracts were even more potent than a commercial grape seed preparation. Similar results were seen in the lipid peroxidation inhibition studies. Our findings also showed a strong correlation of antioxidant activity with the total phenolic content. These extracts when tested for its heavy metals content, were found to be below permissible value for nutraceutical application. In addition, most of the extracts were found not cytotoxic to 3T3 and 4T1 cells at concentrations as high as 100 microg/mL. We conclude that although traditionally these plants are used in the aqueous form, its commercial preparation could be achieved using ethanol since a high total phenolic content and antioxidant activity is associated with this method of preparation.
    Matched MeSH terms: Cytotoxins/pharmacology*
  15. Ong JY, Yong PV, Lim YM, Ho AS
    Life Sci, 2015 Aug 15;135:158-64.
    PMID: 25896662 DOI: 10.1016/j.lfs.2015.03.019
    The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells.
    Matched MeSH terms: Cytotoxins/pharmacology*
  16. Lai SL, Cheah SC, Wong PF, Noor SM, Mustafa MR
    PLoS One, 2012;7(5):e38103.
    PMID: 22666456 DOI: 10.1371/journal.pone.0038103
    BACKGROUND: Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.

    METHODOLOGY/PRINCIPAL FINDINGS: PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.

    CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy.

    Matched MeSH terms: Cytotoxins/pharmacology*
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