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  1. δ- and γ-tocotrienols induce classical ultrastructural apoptotic changes in human T lymphoblastic leukemic cells
    Wong RS, Radhakrishnan AK, Ibrahim TA, Cheong SK
    Microsc Microanal, 2012 Jun;18(3):462-9.
    PMID: 22640960 DOI: 10.1017/S1431927612000177
    Tocotrienols are isomers of the vitamin E family, which have been reported to exert cytotoxic effects in various cancer cells. Although there have been some reports on the effects of tocotrienols in leukemic cells, ultrastructural evidence of tocotrienol-induced apoptotic cell death in leukemic cells is lacking. The present study investigated the effects of three isomers of tocotrienols (alpha, delta, and gamma) on a human T lymphoblastic leukemic cell line (CEM-SS). Cell viability assays showed that all three isomers had cytotoxic effects (p < 0.05) on CEM-SS cells with delta-tocotrienol being the most potent. Transmission electron microscopy showed that the cytotoxic effects by delta- and gamma-tocotrienols were through the induction of an apoptotic pathway as demonstrated by the classical ultrastructural apoptotic changes characterized by peripheral nuclear chromatin condensation and nuclear fragmentation. These findings were confirmed biochemically by the demonstration of phosphatidylserine externalization via flow cytometry analysis. This is the first study showing classical ultrastructural apoptotic changes induced by delta- and gamma-tocotrienols in human T lymphoblastic leukemic cells.
    Matched MeSH terms: Cell Survival/drug effects
  2. Bioassay-guided isolation of neuroprotective compounds from Loranthus parasiticus against H₂O₂-induced oxidative damage in NG108-15 cells
    Wong DZ, Kadir HA, Ling SK
    J Ethnopharmacol, 2012 Jan 6;139(1):256-64.
    PMID: 22107836 DOI: 10.1016/j.jep.2011.11.010
    A parasite plant, Loranthus parasiticus (Loranthaceae), which is generally known as benalu teh (in Malay), Sang Ji Sheng (in Chinese), and baso-kisei (in Japan) distributed in south and southwest part of China, has been used as a folk medicine for the treatment of schizophrenia in southwest China. Loranthus parasiticus has various uses in folk and traditional medicines for bone, brain, kidney, liver, expels wind-damp, and prevents miscarriage.
    Matched MeSH terms: Cell Survival/drug effects
  3. NCI in vitro and in silico anticancer screen, cell cycle pertubation and apoptosis-inducing potential of new acylated, benzylidene and isopropylidene derivatives of andrographolide
    Wong CC, Sagineedu SR, Sumon SH, Sidik SM, Phillips R, Lajis NH, et al.
    Environ Toxicol Pharmacol, 2014 Sep;38(2):489-501.
    PMID: 25168151 DOI: 10.1016/j.etap.2014.07.016
    Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate.
    Matched MeSH terms: Cell Survival/drug effects
  4. In vitro 3D colon tumor penetrability of SRJ09, a new anti-cancer andrographolide analog
    Wong CC, Periasamy N, Sagineedu SR, Sidik S, Sumon SH, Loadman P, et al.
    Invest New Drugs, 2014 Oct;32(5):806-14.
    PMID: 24875131 DOI: 10.1007/s10637-014-0105-6
    Limited tumor penetrability of anti-cancer drugs is recognized as one of the major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2-bromobenzylidene) andrographolide) has been identified as a lead anti-cancer agent for colon cancer. Recently, this compound was shown by us to be a mutant K-Ras binder. In this present study, the penetrability of SRJ09 through the DLD-1 colon cancer multicell layer (MCL) was evaluated. The amount of SRJ09 that penetrated through the MCL was quantitated by utilizing high performance liquid chromatography (HPLC). Histopathological staining was used to visualize the morphology of MCL. A chemosensitivity assay was performed to assess the anti-cancer activity of SRJ09 in DLD-1 cells. SRJ09 was able to penetrate through DLD-1 MCL and is inversely proportional with the MCL thickness. The flow rates for SRJ09 through MCL were 0.90 ± 0.20 μM/min/cm(2) and 0.56 ± 0.06 μM/min/cm(2) for days 1 and 5, respectively, which are better than doxorubicin. Histopathological examination revealed that the integrity of the DLD-1 MCL was retained and no visible damage was inflicted on the cell membrane, confirming the penetration of SRJ09 was by diffusion. Short term exposure (1 h) in DLD-1 cells demonstrated SRJ09 had IC50 of 41 μM which was approximately 4-folds lower than andrographolide, the parent compound of SRJ09. In conclusion, SRJ09 successfully penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to be developed as a clinically viable anti-colon cancer drug.
    Matched MeSH terms: Cell Survival/drug effects
  5. Assessment of anti-inflammatory effect of 5β-hydroxypalisadin B isolated from red seaweed Laurencia snackeyi in zebrafish embryo in vivo model
    Wijesinghe WA, Kim EA, Kang MC, Lee WW, Lee HS, Vairappan CS, et al.
    Environ Toxicol Pharmacol, 2014 Jan;37(1):110-7.
    PMID: 24317194 DOI: 10.1016/j.etap.2013.11.006
    5β-Hydroxypalisadin B, a halogenated secondary metabolite isolated from red seaweed Laurencia snackeyi was evaluated for its anti-inflammatory activity in lipopolysaccharide (LPS)-induced zebrafish embryo. Preliminary studies suggested the effective concentrations of the compound as 0.25, 0.5, 1 μg/mL for further in vivo experiments. 5β-Hydroxypalisadin B, exhibited profound protective effect in the zebrafish embryo as confirmed by survival rate, heart beat rate, and yolk sac edema size. The compound acts as an effective agent against reactive oxygen species (ROS) formation induced by LPS and tail cut. Moreover, 5β-hydroxypalisadin B effectively inhibited the LPS-induced nitric oxide (NO) production in zebrafish embryo. All the tested protective effects of 5β-hydroxypalisadin B were comparable to the well-known anti-inflammatory agent dexamethasone. According to the results obtained, 5β-hydroxypalisadin B isolated from red seaweed L. snackeyi could be considered as an effective anti-inflammatory agent which might be further developed as a functional ingredient.
    Matched MeSH terms: Cell Survival/drug effects
  6. Activity of Eurycoma longifolia root extract against Plasmodium falciparum in vitro
    Wernsdorfer WH, Ismail S, Chan KL, Congpuong K, Wernsdorfer G
    Wien Klin Wochenschr, 2009 Oct;121 Suppl 3:23-6.
    PMID: 19915812 DOI: 10.1007/s00508-009-1230-7
    The habitats of Eurycoma longifolia Jack, a slender tree, are jungles in Malaysia and Indonesia. It belongs to the family Simaroubaceae and is a source of quassinoids with anabolic, antimalarial and cytostatic activity. In this study, conducted during 2008 in Mae Sot, Thailand, a standardized extract of E. longifolia containing three major quassinoids, eurycomanone (1), 13,21-dihydroeurycomanone (2) and 13alpha(21)-epoxyeurycomanone (3) was evaluated for antiplasmodial activity against Plasmodium falciparum and its activity has been compared with that of artemisinin, using 38 fresh parasite isolates and assessment of inhibition of schizont maturation. The IC(50), IC(90) and IC(99) values for artemisinin were 4.30, 45.48 and 310.97 microg/l, and those for the root extract from E. longifolia 14.72, 139.65 and 874.15 microg/l respectively. The GMCOC for artemisinin was 337.81 mug/l, and for the plant extract it was 807.41 microg/l. The log-concentration probit regressions were parallel. The inhibitory activity of the E. longifolia extract was higher than that expected from the three quassinoids isolated from the plant, suggesting synergism between the quassinoids or the presence of other unidentified compounds.
    Matched MeSH terms: Cell Survival/drug effects
  7. Gelam and Nenas honeys inhibit proliferation of HT 29 colon cancer cells by inducing DNA damage and apoptosis while suppressing inflammation
    Wen CT, Hussein SZ, Abdullah S, Karim NA, Makpol S, Mohd Yusof YA
    Asian Pac J Cancer Prev, 2012;13(4):1605-10.
    PMID: 22799375
    Gelam and Nenas monofloral honeys were investigated in this study for their chemopreventive effects against HT 29 colon cancer cells. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolim) assays showed more effective inhibition of colon cancer cells proliferation by Gelam honey with IC₅₀ values of 39.0 mg/ml and 85.5 mg/ml respectively after 24 hours of treatment. Alkali comet assays revealed both honeys increased DNA damage significantly in a dose dependent manner. In addition, annexin V-FITC/PI flow cytometry demonstrated that at IC₅₀ concentrations and above, both Gelam and Nenas honeys induced apoptosis significantlyat values higher than for necrosis (p<0.05). Measurement of prostaglandin E₂ (PGE₂) confirmed that Gelam and Nenas honeys reduced its production in H₂O₂ inflammation-induced colon cancer cells. In conclusion, our study indicated and confirmed that both Gelam and Nenas honeys are capable of suppressing the growth of HT 29 colon cancer cells by inducing apoptosis and suppressing inflammation.
    Matched MeSH terms: Cell Survival
  8. Characterization of anticancer, antimicrobial, antioxidant properties and chemical compositions of Peperomia pellucida leaf extract
    Wei LS, Wee W, Siong JY, Syamsumir DF
    Acta Med Iran, 2011;49(10):670-4.
    PMID: 22071643
    Peperomia pellucida leaf extract was characterized for its anticancer, antimicrobial, antioxidant activities, and chemical compositions. Anticancer activity of P. pellucida leaf extract was determined through Colorimetric MTT (tetrazolium) assay against human breast adenocarcinoma (MCF-7) cell line and the antimicrobial property of the plant extract was revealed by using two-fold broth micro-dilution method against 10 bacterial isolates. Antioxidant activity of the plant extract was then characterized using α, α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging method and the chemical compositions were screened and identified using gas chromatography-mass spectrometry (GC-MS). The results of present study indicated that P. pellucida leaf extract possessed anticancer activities with half maximal inhibitory concentration (IC(50)) of 10.4 ± 0.06 µg/ml. The minimum inhibitory concentration (MIC) values were ranged from 31.25 to 125 mg/l in which the plant extract was found to inhibit the growth of Edwardsiella tarda, Escherichia coli, Flavobacterium sp., Pseudomonas aeruginosa and Vibrio cholerae at 31.25 mg/l; Klebsiella sp., Aeromonas hydrophila and Vibrio alginolyticus at 62.5 mg/l; and it was able to control the growth of Salmonella sp. and Vibrio parahaemolyticus at 125 mg/l. At the concentration of 0.625 ppt, the plant extract was found to inhibit 30% of DPPH, free radical. Phytol (37.88%) was the major compound in the plant extract followed by 2-Naphthalenol, decahydro- (26.20%), Hexadecanoic acid, methyl ester (18.31%) and 9,12-Octadecadienoic acid (Z,Z)-, methyl ester (17.61%). Findings from this study indicated that methanol extract of P. pellucida leaf possessed vast potential as medicinal drug especially in breast cancer treatment.
    Matched MeSH terms: Cell Survival/drug effects
  9. Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam Honey and Ginger Extract via mTOR and Wnt/β-catenin Pathways
    Wee LH, Morad NA, Aan GJ, Makpol S, Wan Ngah WZ, Mohd Yusof YA
    Asian Pac J Cancer Prev, 2015;16(15):6549-56.
    PMID: 26434873
    The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.
    Matched MeSH terms: Cell Survival/drug effects
  10. 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 cell population. The DNA fragmentation assay also showed apoptotic features in the clausenidin-treated HT-29 cells. Clausenidin treatment had caused significant (p cells and mitochondrial ROS and mitochondrial membrane depolarization. The results suggest the involvement of the mitochondria in the caspase-dependent apoptosis in clausenidin-treated colon cancer cells.
    CONCLUSION: Clausenidin induces a caspase-dependent apoptosis in colon cancers through the stimulation of the mitochondria. The study demonstrates the potential of clausenidin for use in the treatment of colon cancers.
    KEYWORDS: Apoptosis; Caspase 9; Clausenidin; Colon cancer; MMP; bax; bcl 2
    Matched MeSH terms: Cell Survival/drug effects
  11. Hypoxia enhances the viability, growth and chondrogenic potential of cryopreserved human adipose-derived stem cells
    Wan Safwani WKZ, Choi JR, Yong KW, Ting I, Mat Adenan NA, Pingguan-Murphy B
    Cryobiology, 2017 04;75:91-99.
    PMID: 28108309 DOI: 10.1016/j.cryobiol.2017.01.006
    Cryopreservation is the only existing method of storage of human adipose-derived stem cells (ASCs) for clinical use. However, cryopreservation has been shown to be detrimental to ASCs, particularly in term of cell viability. To restore the viability of cryopreserved ASCs, it is proposed to culture the cells in a hypoxic condition. To this end, we aim to investigate the effect of hypoxia on the cryopreserved human ASCs in terms of not only cell viability, but also their growth and stemness properties, which have not been explored yet. In this study, human ASCs were cultured under four different conditions: fresh (non-cryopreserved) cells cultured in 1) normoxia (21% O2) and 2) hypoxia (2% O2) and cryopreserved cells cultured in 3) normoxia and 4) hypoxia. ASCs at passage 3 were subjected to assessment of viability, proliferation, differentiation, and expression of stemness markers and hypoxia-inducible factor-1 alpha (HIF-1α). We found that hypoxia enhances the viability and the proliferation rate of cryopreserved ASCs. Further, hypoxia upregulates HIF-1α in cryopreserved ASCs, which in turn activates chondrogenic genes to promote chondrogenic differentiation. In conclusion, hypoxic-preconditioned cryopreserved ASCs could be an ideal cell source for cartilage repair and regeneration.
    Matched MeSH terms: Cell Survival
  12. Fulltext Dose enhancement effects by different size of gold nanoparticles under irradiation of megavoltage photon beam
    Wan Nordiana W Abd Rahman, Raizulnasuha Ab Rashid, Mahfuzah Muhammad, Khairunisak Abdul Razak, Norhayati Dollah, Moshi Geso
    Jurnal Sains Nuklear Malaysia, 2018;30(2):23-29.
    MyJurnal
    Gold nanoparticles (AuNPs) have been extensively investigated as dose enhancement agent to increase the lethal dose to the tumours while minimizing dose to the normal tissue. Their intriguing properties and characteristics such as small size and shape provide favorable option in increasing radiotherapy therapeutic efficiency. In this study, the effects of AuNPs size on the dose enhancement effects irradiated under megavoltage photon beams were investigated. The study was conducted in-vitro on HeLa cells using AuNPs of 5 nm and 15 nm sizes. The cells samples were incubated with AuNPs and irradiated with photon beam of energy 6 MV and 10 MV at 100 cm SSD and 10 cm x 10 cm field size. Clonogenic assay were performed to observe the dose enhancement effects on cell survival. Dose enhancement factor (DEF) were extrapolated and evaluated from the cell survival curves. The results show that both sizes of AuNPs produce dose enhancement with the larger size AuNPs of 15 nm produce more dose enhancement compare to 5 nm AuNPs for 6 MV photon beam. Dose enhancements were observed for 10 MV photon beams but DEF for both sizes AuNPs shows no differences. In conclusion, larger size AuNPs produce higher dose enhancement compare to small size of AuNPs which conclude that nanoparticles size is important factor that need to be taken into account for AuNPs to be applied in radiotherapy.
    Matched MeSH terms: Cell Survival
  13. Fulltext Stimulated Ag Nanoparticles by Pulsed Laser Ablation for Breast Cancer Treatment
    Wan Mohd Shukri WN, Bakhtiar H, Islam S, Bidin N, Baba S, Hamdan S, et al.
    Biomed Environ Sci, 2021 Feb 20;34(2):119-123.
    PMID: 33685570 DOI: 10.3967/bes2021.017
    Matched MeSH terms: Cell Survival/drug effects
  14. An ex vivo culture model for orthodontically induced root resorption
    Wan Hassan WN, Stephenson PA, Waddington RJ, Sloan AJ
    J Dent, 2012 May;40(5):406-15.
    PMID: 22342686 DOI: 10.1016/j.jdent.2012.02.002
    Root resorption is a ubiquitous although undesirable sequela to orthodontic treatment. Current methods to investigate the pathophysiology have certain limitations. In pursuit to understand and develop treatment modalities for orthodontically induced root resorption, the ability to manipulate cells within their natural extracellular matrix in a three dimensional organotypic model is invaluable. The study aimed to develop a laboratory-based organotypic model to investigate the effect of orthodontic forces on the periodontium.
    Matched MeSH terms: Cell Survival/physiology
  15. Fulltext Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic MC3T3-E1 cells: a temporal sequential study
    Wan Hasan WN, Abd Ghafar N, Chin KY, Ima-Nirwana S
    Drug Des Devel Ther, 2018;12:1715-1726.
    PMID: 29942115 DOI: 10.2147/DDDT.S168935
    PURPOSE: Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis. However, detailed studies of the effects of AnTT on preosteoblastic cells were limited. This study was conducted to investigate the osteogenic effect of AnTT on preosteoblast MC3T3-E1 cells in a time-dependent manner.

    MATERIALS AND METHODS: Murine MC3T3-E1 preosteoblastic cells were cultured in the different concentrations of AnTT (0.001-1 µg/mL) up to 24 days. Expression of osteoblastic differentiation markers was measured by qPCR (osterix [OSX], collagen 1 alpha 1 [COL1α1], alkaline phosphatase [ALP], and osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of collagen and mineralized nodules was done via Direct Red staining and Alizarin Red staining, respectively.

    RESULTS: The results showed that osteoblastic differentiation-related genes, such as OSX, COL1α1, ALP, and OCN, were significantly increased in the AnTT-treated groups compared to the vehicle group in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day 3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day 9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was observed in the AnTT-treated groups via increasing Alizarin Red staining from day 3 to day 21 (P<0.05).

    CONCLUSION: Our results suggest that AnTT enhances the osteogenic activity by promoting the bone formation-related genes and proteins in a temporal and sequential manner.

    Matched MeSH terms: Cell Survival/drug effects
  16. Genotoxicity assessment of biphasic calcium phosphate of modified porosity on human dental pulp cells using Ames and Comet assays
    Wahab NFAC, Kannan TP, Mahmood Z, Rahman IA, Ismail H
    Toxicol In Vitro, 2018 Mar;47:207-212.
    PMID: 29247761 DOI: 10.1016/j.tiv.2017.12.002
    Biphasic Calcium Phosphate (BCP) with a ratio of 20/80 Hydroxyapatite (HA)/Beta-tricalcium phosphate (β-TCP) promotes the differentiation of human dental pulp cells (HDPCs). In the current study, the genotoxicity of locally produced BCP of modified porosity (65%) with a mean pore size of 300micrometer (μm) was assessed using Comet and Ames assays. HDPCs were treated with BCP extract at three different inhibitory concentrations which were obtained based on cytotoxicity test conducted with concurrent negative and positive controls. The tail moment of HDPCs treated with BCP extract at all three concentrations showed no significant difference compared to negative control (p>0.05), indicating that BCP did not induce DNA damage to HDPCs. The BCP was evaluated using five tester strains of Salmonella typhimurium TA98, TA100, TA102, TA1537 and TA1538. Each strain was incubated with BCP extract with five different concentrations in the presence and absence of metabolic activation system (S9) mix. Concurrently, negative and positive controls were included. The average number of revertant colonies per plate treated with the BCP extract was less than double as compared to the number of revertant colonies in negative control plate and no dose-related increase was observed. Results from both assays suggested that the BCP of modified porosity did not exhibit any genotoxic effect under the present test conditions.
    Matched MeSH terms: Cell Survival/drug effects
  17. In silico studies, synthesis and anticancer activity of novel diphenyl ether-based pyridine derivatives
    Verma R, Bairy I, Tiwari M, Bhat GV, Shenoy GG
    Mol Divers, 2019 Aug;23(3):541-554.
    PMID: 30430400 DOI: 10.1007/s11030-018-9889-1
    A series of novel 2-amino-4-(3-hydroxy-4-phenoxyphenyl)-6-(4-substituted phenyl) nicotinonitriles were synthesized and evaluated against HepG2, A-549 and Vero cell lines. Compounds 3b (IC50 16.74 ± 0.45 µM) and 3p (IC50 10.57 ± 0.54 µM) were found to be the most active compounds against A-549 cell line among the evaluated compounds. Further 3b- and 3p-induced apoptosis was characterized by AO/EB (acridine orange/ethidium bromide) nuclear staining method and also by DNA fragmentation study. A decrease in cell viability and initiation of apoptosis was clearly evident through the morphological changes in the A-549 cells treated with 3b and 3p when stained with this method. Fragmentation of DNA into nucleosomes was observed which further confirmed the cell apoptosis in cells treated with compound 3b. Flow cytometry studies confirmed the cell cycle arrest at G2/M phase in A549 cells treated with compound 3b. Further in silico studies performed supported the in vitro anticancer activity of these compounds as depicted by dock score and binding energy values.
    Matched MeSH terms: Cell Survival/drug effects
  18. Fulltext Anti-EGFR anchored paclitaxel loaded PLGA nanoparticles for the treatment of triple negative breast cancer. In-vitro and in-vivo anticancer activities
    Venugopal V, Krishnan S, Palanimuthu VR, Sankarankutty S, Kalaimani JK, Karupiah S, et al.
    PLoS One, 2018;13(11):e0206109.
    PMID: 30408068 DOI: 10.1371/journal.pone.0206109
    The aim of the present study is to analyze the viability of anti-EGFR anchored immunonanoparticle (INP) bearing Paclitaxel (PTX) to specifically bind the EGFR protein on the TNBC cells. The NP was prepared by nanoprecipitation and characterized the particle size, charge, entrapment of drug and release of it. The anti-EGFR anchored and the integrity was confirmed by SDS-PAGE. Cytotoxicity and NPs cellular uptake was analyzed with MDA-MB-468 type cancer cells and the EGFR expression was confirmed by PCR, qualitatively and quantitatively. The in-vivo antitumor activity of INP was determined by using athymic mice model and targeting efficiency was measured by calculating the PTX accumulation in the tumor plasma. The prepared INP with the size of 336.3 nm and the charge of -3.48 mV showed sustained drug release upto 48 h. The INP showed significant reduction of cancer cell viability of 10.6% for 48 h with 93 fold higher PTX accumulation in the tumor plasma compared with NPs. Based on these reports, we recommend that anti-EGFR anchored PTX loaded NP may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX for the treatment of TNBC.
    Matched MeSH terms: Cell Survival/drug effects
  19. Zebrafish phenotypic screen identifies novel Notch antagonists
    Velaithan V, Okuda KS, Ng MF, Samat N, Leong SW, Faudzi SM, et al.
    Invest New Drugs, 2017 04;35(2):166-179.
    PMID: 28058624 DOI: 10.1007/s10637-016-0423-y
    Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors. Subsequent secondary screens using HEK293T cells overexpressing truncated Notch1 (HEK293TΔE) identified 2 compounds, EDD3 and 3H4MB, to be potential Notch antagonists. Both compounds reduced protein expression of NOTCH1, Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) in HEK293TΔE and downregulated Notch target genes. Importantly, EDD3 treatment of human oral cancer cell lines demonstrated reduction of Notch target proteins and genes. EDD3 also inhibited proliferation and induced G0/G1 cell cycle arrest of ORL-150 cells through inducing p27KIP1. Our data demonstrates the utility of the zebrafish phenotypic screen and identifying EDD3 as a promising Notch antagonist for further development as a novel therapeutic agent.
    Matched MeSH terms: Cell Survival/drug effects
  20. Microfluidic production of bioactive fibrin micro-beads embedded in crosslinked collagen used as an injectable bulking agent for urinary incontinence treatment
    Vardar E, Larsson HM, Allazetta S, Engelhardt EM, Pinnagoda K, Vythilingam G, et al.
    Acta Biomater, 2018 02;67:156-166.
    PMID: 29197579 DOI: 10.1016/j.actbio.2017.11.034
    Endoscopic injection of bulking agents has been widely used to treat urinary incontinence, often due to urethral sphincter complex insufficiency. The aim of the study was to develop a novel injectable bioactive collagen-fibrin bulking agent restoring long-term continence by functional muscle tissue regeneration. Fibrin micro-beads were engineered using a droplet microfluidic system. They had an average diameter of 140 μm and recombinant fibrin-binding insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1) was covalently conjugated to the beads. A plasmin fibrin degradation assay showed that 72.5% of the initial amount of α2PI1-8-MMP-IGF-1 loaded into the micro-beads was retained within the fibrin micro-beads. In vitro, the growth factor modified fibrin micro-beads enhanced cell attachment and the migration of human urinary tract smooth muscle cells, however, no change of the cellular metabolic activity was seen. These bioactive micro-beads were mixed with genipin-crosslinked homogenized collagen, acting as a carrier. The collagen concentration, the degree of crosslinking, and the mechanical behavior of this bioactive collagen-fibrin injectable were comparable to reference samples. This novel injectable showed no burst release of the growth factor, had a positive effect on cell behavior and may therefore induce smooth muscle regeneration in vivo, necessary for the functional treatment of stress and other urinary incontinences.

    STATEMENT OF SIGNIFICANCE: Urinary incontinence is involuntary urine leakage, resulting from a deficient function of the sphincter muscle complex. Yet there is no functional cure for this devastating condition using current treatment options. Applied physical and surgical therapies have limited success. In this study, a novel bioactive injectable bulking agent, triggering new muscle regeneration at the injection site, has been evaluated. This injectable consists of cross-linked collagen and fibrin micro-beads, functionalized with bound insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1). These bioactive fibrin micro-beads induced human smooth muscle cell migration in vitro. Thus, this injectable bulking agent is apt to be a good candidate for regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for urinary incontinence.

    Matched MeSH terms: Cell Survival
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