Displaying publications 81 - 100 of 853 in total

Abstract:
Sort:
  1. Ahmad WMAW, Yaqoob MA, Noor NFM, Ghazali FMM, Rahman NA, Tang L, et al.
    Biomed Res Int, 2021;2021:5436894.
    PMID: 34904115 DOI: 10.1155/2021/5436894
    Background: Cancer is primarily caused by smoking, alcohol, betel quit, a series of genetic alterations, and epigenetic abnormalities in signaling pathways, which result in a variety of phenotypes that favor the development of OSCC. Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, accounting for 80-90% of all oral malignant neoplasms. Oral cancer is relatively common, and it is frequently curable when detected and treated early enough. The tumor-node-metastasis (TNM) staging system is used to determine patient prognosis; however, geographical inaccuracies frequently occur, affecting management.

    Objective: To determine the additional relationship between factors discovered by searching for sociodemographic and metastasis factors, as well as treatment outcomes, which could help improve the prediction of the survival rate in cancer patients. Material and Methods. A total of 56 patients were recruited from the ambulatory clinic at the Hospital Universiti Sains Malaysia (USM). In this retrospective study, advanced computational statistical modeling techniques were used to evaluate data descriptions of several variables such as treatment, age, and distant metastasis. The R-Studio software and syntax were used to implement and test the hazard ratio. The statistics for each sample were calculated using a combination model that included methods such as bootstrap and multiple linear regression (MLR).

    Results: The statistical strategy showed R demonstrates that regression modeling outperforms an R-squared. It demonstrated that when data is partitioned into a training and testing dataset, the hybrid model technique performs better at predicting the outcome. The variable validation was determined using the well-established bootstrap-integrated MLR technique. In this case, three variables are considered: age, treatment, and distant metastases. It is important to note that three things affect the hazard ratio: age (β 1: -0.006423; p < 2e - 16), treatment (β 2: -0.355389; p < 2e - 16), and distant metastasis (β 3: -0.355389; p < 2e - 16). There is a 0.003469102 MSE for the linear model in this scenario.

    Conclusion: In this study, a hybrid approach combining bootstrapping and multiple linear regression will be developed and extensively tested. The R syntax for this methodology was designed to ensure that the researcher completely understood the illustration. In this case, a hybrid model demonstrates how this critical conclusion enables us to better understand the utility and relative contribution of the hybrid method to the outcome. The statistical technique used in this study, R, demonstrates that regression modeling outperforms R-squared values of 0.9014 and 0.00882 for the predicted mean squared error, respectively. The conclusion of the study establishes the superiority of the hybrid model technique used in the study.

    Matched MeSH terms: Cell Survival/physiology*
  2. Cheng WT, Kantilal HK, Davamani F
    Malays J Med Sci, 2020 Jul;27(4):9-21.
    PMID: 32863742 MyJurnal DOI: 10.21315/mjms2020.27.4.2
    The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC). The enterotoxigenic B. fragilis (ETBF) forms biofilm and produce toxin and play a role in CRC, whereas the non-toxigenic B. fragilis (NTBF) does not produce toxin. The ETBF triggers the expression of cyclooxygenase (COX)-2 that releases PGE2 for inducing inflammation and control cell proliferation. From chronic intestinal inflammation to cancer development, it involves signal transducers and activators of transcription (STAT)3 activation. STAT3 activates by the interaction between epithelial cells and BFT. Thus, regulatory T-cell (Tregs) will activates and reduce interleukin (IL)-2 amount. As the level of IL-2 drops, T-helper (Th17) cells are generated leading to increase in IL-17 levels. IL-17 is implicated in early intestinal inflammation and promotes cancer cell survival and proliferation and consequently triggers IL-6 production that activate STAT3 pathway. Additionally, BFT degrades E-cadherin, hence alteration of signalling pathways can upregulate spermine oxidase leading to cell morphology and promote carcinogenesis and irreversible DNA damage. Patient with familial adenomatous polyposis (FAP) disease displays a high level of tumour load in the colon. This disease is caused by germline mutation of the adenomatous polyposis coli (APC) gene that increases bacterial adherence to the mucosa layer. Mutated-APC gene genotype with ETBF increases the chances of CRC development. Therefore, the colonisation of the ETBF in the intestinal tract depicts tumour aetiology can result in risk of hostility and effect on human health.
    Matched MeSH terms: Cell Survival
  3. Shahrulazua A, Samsudin A, Iskandar M, Amran A
    Malays Orthop J, 2013 Mar;7(1):41-8.
    PMID: 25722806 MyJurnal DOI: 10.5704/MOJ.1303.015
    Despite its claimed therapeutic effects, the action of sea cucumber (known as gamat in the Malay language) on human osteoblast cells is still unknown. We performed in vitro studies utilising extract of Stichopus sp1 (gamat) to elucidate its effects on cell viability and functional activity. We found an inverse relationship between gamat concentration and its effect on osteoblast cell viability (p<0.001). Only gamat concentration at 1mg/ml significantly promoted cell viability at day 3 of incubation. There was a trend towards increased osteoblast cell function in the presence of gamat at 5mg/ml and 10mg/ml but this observation was not consistent at different incubation periods.
    Matched MeSH terms: Cell Survival
  4. Husin F, Chan YY, Gan SH, Sulaiman SA, Shueb RH
    PMID: 25767554 DOI: 10.1155/2015/596109
    Objective. To investigate the potential effect of Hydrocotyle sibthorpioides Lam. (H. sibthorpioides) extracts against in vitro dengue viral replication. Methods. The cytotoxicity of H. sibthorpioides was evaluated using a cell viability assay. Cells were pre- and posttreated with water and methanol extracts of H. sibthorpioides, and the viral inhibitory effect was investigated by observing the morphological changes, which were further confirmed by plaque assay. Results. The methanolic extract cytotoxicity was higher in Vero and C6/36 cells than the cytotoxicity of the water extract. Preincubation of the cells with H. sibthorpioides extract showed nonexistent to mild prophylactic effects. The posttreatment of Vero cells with H. sibthorpioides methanolic extract presented higher antidengue activities when compared with the water extract. Surprisingly, posttreatment of C6/36 cells resulted in an enhancement of viral replication. Conclusion. H. sibthorpioides had variable effects on dengue viral replication, depending on the treatment, cell lines, and solvent types. This study provides important novel insights on the phytomedicinal properties of H. sibthorpioides extracts on dengue virus.
    Matched MeSH terms: Cell Survival
  5. Zheng X, Liao Y, Wang J, Hu S, Rudramurthy GR, Swamy MK, et al.
    PMID: 30524484 DOI: 10.1155/2018/9691085
    Microglial cells, upon hyperactivation, produce proinflammatory cytokines and other oxidative stress mediators causing neuroinflammation, which is associated with the progress of many neurodegenerative diseases. Suppressing the microglial activation has hence been used as an approach for treating such diseases. In this study, the antineuroinflammatory effect of simvastatin was examined in lipopolysaccharide (LPS)-activated rat C6 glioma cells. The cell proliferation and cytotoxic effect of LPS and simvastatin on C6 glioma cells was evaluated by (MTT) assay. Neuroinflammation was induced in differentiated cell lines by treatment with 3.125 μg/mL of LPS for 12 h. Upon induction, the cell lines were treated with different concentrations (3.125, 6.25, 12.5, 25, 50, 100 μM) of simvastatin and incubated in a humidified CO2 incubator for 24 to 48 h. The optimum concentrations of LPS and simvastatin were found to be 3.125 μg/mL and 25 μM, respectively, with a cell viability of more than 90% at 24 h postincubation. Furthermore, proinflammatory marker expression was analyzed by flow cytometry and showed a decrease in interferon-γ, interleukin 6, nuclear factor-κB p65, and tumor necrosis factor-α in simvastatin-treated and LPS-induced neuroinflammatory cells, and the mean fluorescent values were found to be 21.75 ± 0.76, 20.9 ± 1.90, 19.72 ± 1.29, and 16.82 ± 0.97, respectively, as compared to the untreated cells. Thus, we show that simvastatin has the potential to regulate the anti-inflammatory response in microglial cells upon LPS challenge. Hence, simvastatin can be employed as a potent anti-inflammatory drug against neuroinflammatory diseases and neurodegenerative disorders.
    Matched MeSH terms: Cell Survival
  6. Umar MI, Hassan W, Murtaza G, Buabeid M, Arafa E, Irfan HM, et al.
    Pathol Oncol Res, 2021;27:1609828.
    PMID: 34588926 DOI: 10.3389/pore.2021.1609828
    A hormonal imbalance may disrupt the rigorously monitored cellular microenvironment by hampering the natural homeostatic mechanisms. The most common example of such hormonal glitch could be seen in obesity where the uprise in adipokine levels is in virtue of the expanding bulk of adipose tissue. Such aberrant endocrine signaling disrupts the regulation of cellular fate, rendering the cells to live in a tumor supportive microenvironment. Previously, it was believed that the adipokines support cancer proliferation and metastasis with no direct involvement in neoplastic transformations and tumorigenesis. However, the recent studies have reported discrete mechanisms that establish the direct involvement of adipokine signaling in tumorigenesis. Moreover, the individual adipokine profile of the patients has never been considered in the prognosis and staging of the disease. Hence, the present manuscript has focused on the reported extensive mechanisms that culminate the basis of poor prognosis and diminished survival rate in obese cancer patients.
    Matched MeSH terms: Cell Survival/physiology*
  7. Ng CH, Wang WS, Chong KV, Win YF, Neo KE, Lee HB, et al.
    Dalton Trans, 2013 Jul 28;42(28):10233-43.
    PMID: 23728518 DOI: 10.1039/c3dt50884f
    Chiral enantiomers [Cu(phen)(L-threo)(H2O)]NO3 1 and [Cu(phen)(D-threo)(H2O)]NO3 2 (threo = threoninate) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(II) complexes, viz. L- and D-[Cu(phen)(5MeOCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; 5MeOCA = 5-methyloxazolidine-4-carboxylate; x = 0-3) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-Visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. Analysis of restriction enzyme inhibition by these four complexes revealed modulation of DNA binding selectivity by the type of ligand, ligand modification and chirality. Their interaction with bovine serum albumin was investigated by FL and electronic spectroscopy. With the aid of the crystal structure of BSA, spectroscopic evidence suggested their binding at the cavity containing Trp134 with numerous Tyr residues in subdomain IA. The products were more antiproliferative than cisplatin against cancer cell lines HK-1, MCF-7, HCT116, HSC-2 and C666-1 except HL-60, and were selective towards nasopharyngeal cancer HK-1 cells over normal NP69 cells of the same organ type.
    Matched MeSH terms: Cell Survival/drug effects
  8. Abdul Rahman SF, Xiang Lian BS, Mohana-Kumaran N
    Future Oncol, 2020 Oct;16(28):2235-2249.
    PMID: 32715755 DOI: 10.2217/fon-2020-0389
    The B-cell lymphoma 2 (BCL-2) anti-apoptotic proteins have become attractive therapeutic targets especially with the development of BH3-mimetics which selectively target these proteins. However, it is important to note that expression levels of the anti-apoptotic proteins and their relevance in inhibiting apoptosis varies between different cell lineages. This addiction to certain anti-apoptotic proteins for survival, can be determined with various techniques and targeted effectively with selective BH3-mimetics. Studies have highlighted that anti-apoptotic proteins BCL-XL and MCL-1 are crucial for cervical cancer cell survival. Co-targeting BCL-XL and MCL-1 with selective BH3-mimetics yielded promising results in cervical cancer cell lines. In this review, we focus on the expression levels of the anti-apoptotic proteins in cervical cancer tissues and how to possibly target them with BH3-mimetics.
    Matched MeSH terms: Cell Survival/drug effects; Cell Survival/genetics
  9. Lim DV, Woo WH, Lim JX, Loh XY, Soh HT, Lim SYA, et al.
    Curr Mol Pharmacol, 2024;17(1):e140923221042.
    PMID: 37711005 DOI: 10.2174/1874467217666230914090621
    BACKGROUND: Mutations in the TP53 gene are the most common among genetic alterations in human cancers, resulting in the formation of mutant p53 protein (mutp53). Mutp53 promotes proliferation, migration, invasion, and metastasis in cancer cells. Not only does the initiation of oncogenesis ensue due to mutp53, but resistance towards chemotherapy and radiotherapy in cancer cells also occurs. This review aims to summarise and discuss the oncogenesis of mutant p53 in cancer cells and introduce the various mutant p53 inhibitors currently being evaluated at the pre-clinical and clinical stages. Compounds that induce the wild-type conformation on the targeted p53 missense mutation, restore or enhance the DNA binding of mutant p53, and inhibit cancer cells' growth are highlighted. In addition, the progression and development of the mutant p53 inhibitors in clinical trials are updated.

    CONCLUSION: The progress of developing a cancer treatment that may successfully and efficiently target mutant p53 is on the verge of development. Mutant p53 proteins not only initiate oncogenesis but also cause resistance in cancer cells to certain chemo or radiotherapies, further endorse cancer cell survival and promote migration as well as metastasis of cancerous cells. With this regard, many mutant p53 inhibitors have been developed, some of which are currently being evaluated at the pre-clinical level and have been identified and discussed. To date, APR-246 is the most prominent one that has progressed to the Phase III clinical trial.

    Matched MeSH terms: Cell Survival
  10. Ashaie MA, Islam RA, Kamaruzman NI, Ibnat N, Tha KK, Chowdhury EH
    Pharmaceutics, 2019 Jul 02;11(7).
    PMID: 31269666 DOI: 10.3390/pharmaceutics11070309
    While several treatment strategies are applied to cure breast cancer, it still remains one of the leading causes of female deaths worldwide. Since chemotherapeutic drugs have severe side effects and are responsible for development of drug resistance in cancer cells, gene therapy is now considered as one of the promising options to address the current treatment limitations. Identification of the over-expressed genes accounting for constitutive activation of certain pathways, and their subsequent knockdown with specific small interfering RNAs (siRNAs), could be a powerful tool in inhibiting proliferation and survival of cancer cells. In this study, we delivered siRNAs against mRNA transcripts of over-regulated cell adhesion molecules such as catenin alpha 1 (CTNNA1), catenin beta 1 (CTNNB1), talin-1 (TLN1), vinculin (VCL), paxillin (PXN), and actinin-1 (ACTN1) in human (MCF-7 and MDA-MB-231) and murine (4T1) cell lines as well as in the murine female Balb/c mice model. In order to overcome the barriers of cell permeability and nuclease-mediated degradation, the pH-sensitive carbonate apatite (CA) nanocarrier was used as a delivery vehicle. While targeting CTNNA1, CTNNB1, TLN1, VCL, PXN, and ACTN1 resulted in a reduction of cell viability in MCF-7 and MDA-MB-231 cells, delivery of all these siRNAs via carbonate apatite (CA) nanoparticles successfully reduced the cell viability in 4T1 cells. In 4T1 cells, delivery of CTNNA1, CTNNB1, TLN1, VCL, PXN, and ACTN1 siRNAs with CA caused significant reduction in phosphorylated and total AKT levels. Furthermore, reduced band intensity was observed for phosphorylated and total MAPK upon transfection of 4T1 cells with CTNNA1, CTNNB1, and VCL siRNAs. Intravenous delivery of CTNNA1 siRNA with CA nanoparticles significantly reduced tumor volume in the initial phase of the study, while siRNAs targeting CTNNB1, TLN1, VCL, PXN, and ACTN1 genes significantly decreased the tumor burden at all time points. The tumor weights at the end of the treatments were also notably smaller compared to CA. This successfully demonstrates that targeting these dysregulated genes via RNAi and by using a suitable delivery vehicle such as CA could serve as a promising therapeutic treatment modality for breast cancers.
    Matched MeSH terms: Cell Survival
  11. Yunus U, Zulfiqar MA, Ajmal M, Bhatti MH, Chaudhry GE, Muhammad TST, et al.
    Biomed Mater, 2020 09 26;15(6):065004.
    PMID: 32442994 DOI: 10.1088/1748-605X/ab95e1
    Gemcitabine (GEM) is used to treat various cancers such as breast, pancreatic, non-small lung, ovarian, bladder, and cervical cancers. GEM, however, has the problem of non-selectivity. Water-soluble, fluorescent, and mono-dispersed carbon dots (CDs) were fabricated by ultrasonication of sucrose. The CDs were further conjugated with GEM through amide linkage. The physical and morphological properties of these carbon dot-gemcitabine (CD-GEM) conjugates were determined using different analytical techniques. In vitro cytotoxicity and apoptosis studies of CD-GEM conjugates were evaluated by various bioactivity assays on human cell lines, MCF-7 (human breast adenocarcinoma), and HeLa (cervical cancer) cell lines. The results of kinetic studies have shown a maximum drug loading efficacy of 17.0 mg of GEM per 50.0 mg of CDs. The CDs were found biocompatible, and the CD-GEM conjugates exhibited excellent bioactivity and exerted potent cytotoxicity against tumor cells with an IC50 value of 19.50 μg ml-1 in HeLa cells, which is lower than the IC50 value of pure GEM (∼20.10 μg ml-1). In vitro studies on CD-GEM conjugates demonstrated the potential to replace the conventional administration of GEM. CD-GEM conjugates are more stable, have a higher aqueous solubility, and are more cytotoxic as compared to GEM alone. The CD-GEM conjugates show reduced side effects in the normal cells along with excellent cellular uptake. Hence, CD-GEM conjugates are more selective toward cancerous cell lines as compared to non-cancerous cells. Also, the CD-GEM conjugates successfully induced early and late apoptosis in cancer cell lines and might be effective and safe to use for in vivo applications.
    Matched MeSH terms: Cell Survival/drug effects
  12. Kue CS, Kamkaew A, Lee HB, Chung LY, Kiew LV, Burgess K
    Mol Pharm, 2015 Jan 5;12(1):212-22.
    PMID: 25487316 DOI: 10.1021/mp5005564
    This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for (1)O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC- cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC--photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC- tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC- tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs.
    Matched MeSH terms: Cell Survival
  13. Karimian H, Mohan S, Moghadamtousi SZ, Fadaeinasab M, Razavi M, Arya A, et al.
    Molecules, 2014 Jul 03;19(7):9478-501.
    PMID: 24995928 DOI: 10.3390/molecules19079478
    Tanacetum polycephalum (L.) Schultz-Bip (Mokhaleseh) has been traditionally used in the treatment of headaches, migraines, hyperlipidemia and diabetes. The present study aimed to evaluate its anticancer properties and possible mechanism of action using MCF7 as an in vitro model. T. polycephalum leaves were extracted using hexane, chloroform and methanol solvents and the cytotoxicity was evaluated using the MTT assay. Detection of the early apoptotic cells was investigated using acridine orange/propidium iodide staining. An Annexin-V-FITC assay was carried out to observe the phosphatidylserine externalization as a marker for apoptotic cells. High content screening was applied to analyze the cell membrane permeability, nuclear condensation, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed by using caspase-8, caspase-9 and DNA laddering assays. In addition, Bax/Bcl-2 expressions and cell cycle arrest also have been investigated. MTT assay revealed significant cytotoxicity of T. Polycephalum hexane extract (TPHE) on MCF7 cells with the IC50 value of 6.42±0.35 µg/mL. Significant increase in chromatin condensation was also observed via fluorescence analysis. Treatment of MCF7 cells with TPHE encouraged apoptosis through reduction of MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering the cytochrome c leakage from mitochondria to the cytosol. The treated MCF7 cells significantly arrested at G1 phase. The chromatographic analysis elicited that the major active compound in this extract is 8β-hydroxy-4β,15-dihydrozaluzanin C. Taken together, the results presented in this study demonstrated that the hexane extract of T. Polycephalum inhibits the proliferation of MCF7 cells, resulting in the cell cycle arrest and apoptosis, which was explained to be through the mitochondrial pathway.
    Matched MeSH terms: Cell Survival
  14. How CW, Rasedee A, Manickam S, Rosli R
    Colloids Surf B Biointerfaces, 2013 Dec 1;112:393-9.
    PMID: 24036474 DOI: 10.1016/j.colsurfb.2013.08.009
    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.
    Matched MeSH terms: Cell Survival/drug effects
  15. Chong UR, Abdul-Rahman PS, Abdul-Aziz A, Hashim OH, Junit SM
    PLoS One, 2012;7(6):e39476.
    PMID: 22724021 DOI: 10.1371/journal.pone.0039476
    The plasma cholesterol and triacylglycerol lowering effects of Tamarindus indica extract have been previously described. We have also shown that the methanol extract of T. indica fruit pulp altered the expression of lipid-associated genes including ABCG5 and APOAI in HepG2 cells. In the present study, effects of the same extract on the release of proteins from the cells were investigated using the proteomics approach.
    Matched MeSH terms: Cell Survival/drug effects
  16. Sudi SB, Tanaka T, Oda S, Nishiyama K, Nishimura A, Sunggip C, et al.
    Sci Rep, 2019 07 05;9(1):9785.
    PMID: 31278358 DOI: 10.1038/s41598-019-46252-2
    Myocardial atrophy, characterized by the decreases in size and contractility of cardiomyocytes, is caused by severe malnutrition and/or mechanical unloading. Extracellular adenosine 5'-triphosphate (ATP), known as a danger signal, is recognized to negatively regulate cell volume. However, it is obscure whether extracellular ATP contributes to cardiomyocyte atrophy. Here, we report that ATP induces atrophy of neonatal rat cardiomyocytes (NRCMs) without cell death through P2Y2 receptors. ATP led to overproduction of reactive oxygen species (ROS) through increased amount of NADPH oxidase (Nox) 2 proteins, due to increased physical interaction between Nox2 and canonical transient receptor potential 3 (TRPC3). This ATP-mediated formation of TRPC3-Nox2 complex was also pathophysiologically involved in nutritional deficiency-induced NRCM atrophy. Strikingly, knockdown of either TRPC3 or Nox2 suppressed nutritional deficiency-induced ATP release, as well as ROS production and NRCM atrophy. Taken together, we propose that TRPC3-Nox2 axis, activated by extracellular ATP, is the key component that mediates nutritional deficiency-induced cardiomyocyte atrophy.
    Matched MeSH terms: Cell Survival
  17. Zhang D, Gao C, Li R, Zhang L, Tian J
    Arch Pharm Res, 2017 May;40(5):579-591.
    PMID: 28211011 DOI: 10.1007/s12272-017-0899-9
    2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62. Further analysis illustrated that TEOA promoted the phosphorylation of PERK and elF2α, followed by up-regulation of the downstream protein CHOP, suggesting the involvement of PERK/eIF2α/CHOP pathway and ER stress in TEOA-induced autophagy in SW620 cells. Meanwhile, TEOA-mediated PINK1, Parkin, ubiquitin and p62 activation revealed that TEOA induced specific autophagy-mitophagy in SW620 cells. Additionally, an antioxidant NAC attenuated the TEOA-induced mitophagy, indicating that TEOA triggers mitophagy via a ROS-dependent pathway. Collectively, our findings revealed a novel cellular mechanism of TEOA in the colon cancer cell line SW620, thus providing a molecular basis for developing TEOA into an anti-tumor candidate.
    Matched MeSH terms: Cell Survival/drug effects
  18. Anwar A, Siddiqui R, Hameed A, Shah MR, Khan NA
    Med Chem, 2020;16(7):841-847.
    PMID: 31544702 DOI: 10.2174/1573406415666190722113412
    BACKGROUND: Acanthamoeba is an opportunistic pathogen widely spread in the environment. Acanthamoeba causes excruciating keratitis which can lead to blindness. The lack of effective drugs and its ability to form highly resistant cyst are one of the foremost limitations against successful prognosis. Current treatment involves mixture of drugs at high doses but still recurrence of infection can occur due to ineffectiveness of drugs against the cyst form. Pyridine and its natural and synthetic derivatives are potential chemotherapeutic agents due to their diverse biological activities.

    OBJECTIVE: To study the antiamoebic effects of four novel synthetic dihydropyridine (DHP) compounds against Acanthamoeba castellanii belonging to the T4 genotype. Furthermore, to evaluate their activity against amoeba-mediated host cells cytopathogenicity as well as their cytotoxicity against human cells.

    METHODS: Dihydropyridines were synthesized by cyclic dimerization of alkylidene malononitrile derivatives. Four analogues of functionally diverse DHPs were tested against Acanthamoeba castellanii by using amoebicidal, encystation and excystation assays. Moreover, Lactate dehydrogenase assays were carried out to study cytopathogenicity and cytotoxicity against human cells.

    RESULTS: These compounds showed significant amoebicidal and cysticidal effects at 50 μM concentration, whereas, two of the DHP derivatives also significantly reduced Acanthamoebamediated host cell cytotoxicity. Moreover, these DHPs were found to have low cytotoxicity against human cells suggesting a good safety profile.

    CONCLUSION: The results suggest that DHPs have potential against Acanthamoeba especially against the more resistant cyst stage and can be assessed further for drug development.

    Matched MeSH terms: Cell Survival/drug effects
  19. Fani S, Kamalidehghan B, Lo KM, Hashim NM, Chow KM, Ahmadipour F
    Drug Des Devel Ther, 2015;9:6191-201.
    PMID: 26648695 DOI: 10.2147/DDDT.S87064
    A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.
    Matched MeSH terms: Cell Survival/drug effects
  20. Khan KM, Qurban S, Salar U, Taha M, Hussain S, Perveen S, et al.
    Bioorg Chem, 2016 10;68:245-58.
    PMID: 27592296 DOI: 10.1016/j.bioorg.2016.08.010
    Current study based on the synthesis of new thiazole derivatives via "one pot" multicomponent reaction, evaluation of their in vitro α-glucosidase inhibitory activities, and in silico studies. All synthetic compounds were fully characterized by (1)H NMR, (13)C NMR and EIMS. CHN analysis was also performed. These newly synthesized compounds showed activities in the range of IC50=9.06±0.10-82.50±1.70μM as compared to standard acarbose (IC50=38.25±0.12μM). It is worth mentioning that most of the compounds such as 1 (IC50=23.60±0.39μM), 2 (IC50=22.70±0.60μM), 3 (IC50=22.40±0.32μM), 4 (IC50=26.5±0.40μM), 6 (IC50=34.60±0.60μM), 7 (IC50=26.20±0.43μM), 8 (IC50=14.06±0.18μM), 9 (IC50=17.60±0.28μM), 10 (IC50=27.16±0.41μM), 11 (IC50=19.16±0.19μM), 12 (IC50=9.06±0.10μM), 13 (IC50=12.80±0.21μM), 14 (IC50=11.94±0.18μM), 15 (IC50=16.90±0.20μM), 16 (IC50=12.60±0.14μM), 17 (IC50=16.30±0.29μM), and 18 (IC50=32.60±0.61μM) exhibited potent inhibitory potential. Molecular docking study was performed in order to understand the molecular interactions between the molecule and enzyme. Newly identified α-glucosidase inhibitors except few were found to be completely non-toxic.
    Matched MeSH terms: Cell Survival/drug effects
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links