• Title/Summary/Keyword: viability loss

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Activation of JNK/p38 Pathway is Responsible for α-Methyl-n-butylshikonin Induced Mitochondria-Dependent Apoptosis in SW620 Human Colorectal Cancer Cells

  • Wang, Hai-Bing;Ma, Xiao-Qiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6321-6326
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    • 2014
  • ${\alpha}$-Methyl-n-butylshikonin (MBS), one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we assess the molecular mechanisms of MBS in causing apoptosis of SW620 cells. MBS reduced the cell viability of SW620 cells in a dose-and time-dependent manner and induced cell apoptosis. Treatment of SW620 cells with MBS down-regulated the expression of Bcl-2 and up-regulated the expression of Bak and caused the loss of mitochondrial membrane potential. Additionally, MBS treatment led to activation of caspase-9, caspase-8 and caspase-3, and cleavage of PARP, which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. MBS also induced significant elevation in the phosphorylation of JNK and p38. Pretreatment of SW620 cells with specific inhibitors of JNK (SP600125) and p38 (SB203580) abrogated MBS-induced apoptosis. Our results demonstrated that MBS inhibited growth of colorectal cancer SW620 cells by inducing JNK and p38 signaling pathway, and provided a clue for preclinical and clinical evaluation of MBS for colorectal cancer therapy.

Apoptotic Effects of the B Subunit of Bacterial Cytolethal Distending Toxin on the A549 Lung Cancer Cell Line

  • Yaghoobi, Hajar;Bandehpour, Mojgan;Kazemi, Bahram
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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    • pp.299-304
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    • 2016
  • Cytolethal distending toxin (CDT) is a secreted tripartite genotoxin produced by many pathogenic gram-negative bacteria. It is composed of three subunits, CdtA, CdtB and CdtC, and CdtB-associated deoxyribonuclease (DNase) activity is essential for the CDT toxicity. In the present study, to design a novel potentially antitumor drug against lung cancer, the possible mechanisms of cdtB anticancer properties were explored in the A549 human lung adenocarcinoma cell line. A recombinant plasmid pcDNA3.1/cdtB was constructed expressing CdtB of human periodontal bacterium Aggregatibacter actinomycetemcomitans and investigated for toxic properties in A549 cells and possible mechanisms. It was observed that plasmid pcDNA3.1/cdtB caused loss of cell viability, morphologic changes and induction of apoptosis. Furthermore, measurement of caspase activity indicated involvement of an intrinsic pathway of cell apoptosis. Consequently, the recombinant plasmid pcDNA3.1/cdtB may have potential as a new class of therapeutic agent for gene therapy of lung cancer.

Alteration in cellular acetylcholine influences dauer formation in Caenorhabditis elegans

  • Lee, Jeeyong;Kim, Kwang-Youl;Paik, Young-Ki
    • BMB Reports
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    • v.47 no.2
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    • pp.80-85
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    • 2014
  • Altered acetylcholine (Ach) homeostasis is associated with loss of viability in flies, developmental defects in mice, and cognitive deficits in human. Here, we assessed the importance of Ach in Caenorhabditis elegans development, focusing on the role of Ach during dauer formation. We found that dauer formation was disturbed in choline acetyltransferase (cha-1) and acetylcholinesterase (ace) mutants defective in Ach biosynthesis and degradation, respectively. When examined the potential role of G-proteins in dauer formation, goa-1 and egl-30 mutant worms, expressing mutated versions of mammalian $G_o$ and $G_q$ homolog, respectively, showed some abnormalities in dauer formation. Using quantitative mass spectrometry, we also found that dauer larvae had lower Ach content than did reproductively grown larvae. In addition, a proteomic analysis of acetylcholinesterase mutant worms, which have excessive levels of Ach, showed differential expression of metabolic genes. Collectively, these results indicate that alterations in Ach release may influence dauer formation in C. elegans.

Antimicrobial Activity of Vaccinium macrocarpon (Cranberry) Produced Proanthocyanidin (PAC) on the Growth and Adhesion Properties of Staphylococcus aureus

  • Hui, Jonathan;Choy, John;Suwandaratne, Sid P.;Shervill, Jenna;Gan, Bing S.;Howard, Jeffrey C.;Reid, Gregor
    • Preventive Nutrition and Food Science
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    • v.9 no.1
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    • pp.29-33
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    • 2004
  • Cranberries have long been used by lay people to relieve the symptoms of urinary tract infections. Recent research has determined that the component of cranberry called proanthocyanidin (PAC) is the primary mechanism for inhibiting P-fimbriated E.coli adhesion to uroepithelial cells in vitro. A series of experiments were performed to determine the effects of PAC on growth and adhesion of uropathogenic E. coli and Staphylococcus aureus to urinary catheter material. The results showed that PAC-inhibited binding of Gram positive S. aureus to collagen coated surfaces and significantly decreased the growth of these bacteria. P-fimbriated E.coli did not bind well to the biomaterial and their growth was unaffected by the cranberry extract with the exception of some loss in viability at 1000 $\mu\textrm{g}$/mL after 5 to 18 hours of exposure. This is the first report of the potential for cranberries to interfere with the adhesion and growth of S. aureus, a multi-drug resistant organisms responsible for morbidity and mortality especially in hospitalized patients.

Hinged multiperforator-based extended dorsalis pedis adipofascial flap for dorsal foot defects

  • Abd Al Moktader, Magdy A.
    • Archives of Plastic Surgery
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    • v.47 no.4
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    • pp.340-346
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    • 2020
  • Background Adipofascial flaps covered with a skin graft address the challenges involved in reconstructing dorsal foot defects. The purpose of this study was to describe a large adipofascial flap based on the perforators of the dorsalis pedis artery for large foot defects. Methods Twelve patients aged 5-18 years with large soft tissue defects of the dorsal foot due to trauma were treated with an extended dorsalis pedis adipofascial flap from May 2016 to December 2018. The flap was elevated from the non-injured half of the dorsum of the foot. Its length was increased by fascial extension from the medial or lateral foot fascia to the plantar fascia to cover the defect. All perforators of the dorsalis pedis artery were preserved to increase flap viability. The dorsalis pedis artery and its branches were kept intact. Results The right foot was affected in 10 patients, and the left foot in two patients. All flaps survived, providing an adequate contour and durable coverage with a thin flap. Follow-up lasted up to 2 years, and patients were satisfied with the results. They were able to wear shoes. Donor-site morbidity was negligible. Two cases each of partial skin graft loss and superficial necrosis at the tip of the donor cutaneous flap occurred and were healed by a dressing. Conclusions The hinged multiperforator-based extended dorsalis pedis adipofascial flap described herein is a suitable method for reconstructing dorsal foot defects, as it provides optimal functional and aesthetic outcomes with minimal donor site morbidity.

Induction of Apoptosis with Kigelia africana fruits in HCT116 Human Colon Cancer Cells via MAPKs Signaling Pathway

  • Guon, Tae-Eun;Chung, Ha Sook
    • Natural Product Sciences
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    • v.22 no.3
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    • pp.209-215
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    • 2016
  • Kigelia africana (Lam.) Benth. (Bignoniaceae) is a flowering plants in South, Central and West Africa and commonly known as the sausage tree (Eng.); worsboom (Afr.); umVunguta, umFongothi (Zulu); Modukguhlu (North Sotho); Muvevha (Venda). The dried, powdered fruits are used as dressing for wounds and ulcers, haemorrhoids, rheumatism, purgative, skin-firming, lactation in breast-feeding mothers. The aim of this study is to investigate the cytotoxic and apoptotic potentials of 70% ethanolic extracts of Kigelia africana fruits in HCT116 human colon cancer cells. Treatment of Kigelia africana fruits with various concentrations resulted in a sequence of characteristic of apoptosis, including loss of cell viability and morphological changes. Flow cytometry analysis showed Kigelia africana fruits increased the sub-G1 phase (apoptosis) population. Apoptosis confirmed by annexin V-fluorescein isothiocyanate and propidium iodide double staining in HCT116 human colon cancer cell lines. Moreover, analysis of the mechanism indicated that Kigelia africana fruits showed an increased Bax and Bcl-2 expressions in a dose-dependent manner, resulting in activation of hallmarks of apoptotic events, caspase-3, caspase-9 and cleaved poly-ADP-ribose polymerase. This is the first report to demonstrate the cytotoxicity of Kigelia africana fruits on HCT116 human colon cancer cells.

Neuroprotective Effects of Some Plant Extracts Against Dopamine-induced Oxidative Stress on Neuronal Cell (Dopamine에 의해 산화적 스트레스를 받은 Neuronal Cell에 뇌 보호 효과를 가지는 수종 생약추출물의 검색)

  • Koo, Uk;Lee, Hak-Ju;Lee, Dong-Ho;Lee, Hyun-Jung;Ham, Ah-Rom;Mar, Woong-Chon
    • Korean Journal of Pharmacognosy
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    • v.40 no.1
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    • pp.41-45
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    • 2009
  • Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzhemier's disease. Neuropathologically, PD is characterized by the selective loss of dopaminergic neurons. The neuronal toxicity of cytosolic excess dopamine (DA) has been described in many studies using several cell lines. In dopaminergic neurons, cytosolic excess DA is easily oxidized via monoamine oxidase (MAO)-B, tyrosinase or by auto-oxidation to produce neurotoxic metabolites such as DA quinone. So, in the present study, we induced cell death by treatment of DA ($600{\mu}M$) in human neuroblastoma SH-SY5Y cell which was treated samples before 24 hr, and cell viability was measured by fluorescence activated cell sorter (FACs) analysis. Of those tested, the extracts of Poria cocos (赤茯笭)(whole), Gastrodia elata (rhizomes), Eucommia ulmoides (炒)(barks), Syneilesis palmata (whole), Acorus gramineus (rhizomes), Ligustrum japonicum (leaves) showed neuroprotective effects in dose dependent manner.

Effect of EGF against Oxygen Radical-Induced Neurotoxicity in Cultured Spinal Dorsal Root Ganglion Neurons of Mouse (산소자유기에 의해 저해된 배양 척수감각 신경절 세포에 대한 상피세포성장인자의 영향)

  • Park, Seung-Taeck;Kim, Hyung-Ryong;Chae, Han-Jung
    • YAKHAK HOEJI
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    • v.41 no.1
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    • pp.99-104
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    • 1997
  • In order to elucidate the cytotoxic effect of oxygen radicals on cultured spinal dorsal root ganglion(DRG) neurons derived from mouse. the neurotoxic effect of oxygen radicals w as examined after cultured DRG neurons were exposed to xanthine oxidase(XO) and hypoxanthine(HX)-oxygen radical generating system. In addition. neuroprotective effect of epidermal growth factor(EGF) against oxidant-induced neurotoxicity was also evaluated in these cultures. The results were, as follows: 1. Lethal concentration 50(LC$_{50}$) was 35mU/ml XO and 0.1mM HX in cultured DRG neurons. 2. Oxygen radicals induced the morphological changes such as the decrease of cell number and loss of neurites in these cultures. 3. EGF increased the cell viability and neurofilament in neurons damaged by oxygen radicals. From above the results, it is suggested that oxygen radicals have a cytotoxic effect on cultured DRG neurons of neonatal mouse and selective neurotrophic factors such as EGF are, effective, in blocking the neurotoxicity induced by oxygen radicals in cultured spinal DRG neurons.

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Menadione-induced Cytotoxicity in Rat Platelets: Absence of the Detoxifying Enzyme, Quinone Reductase

  • Kim, Kyung-Ah;Kim, Mee-Jeong;Ryu, Chung-Kyu;Chang, Moon-Jeong;Chung, Jin-Ho
    • Archives of Pharmacal Research
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    • v.18 no.4
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    • pp.256-261
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    • 1995
  • The elevation of intracellular $Ca^{2+}$ in various tissue through oxidative stress induced by menadione has been well documented. Increase of $Ca^{2+}$ level inplatelets results in aggreaction of patelets. To test the hypothesis that menadione-induced $Ca^{2+}$ elevations can play a role in platelet aggregation, we have studied the effect of menadione on aggragation of platelets isolated from female rats. Treatment with menadione to platelet rich plasma (PRP), which proved to be 60% as determined by aggregometry. however, exposure of PRP to menadione leads to a loss of cell viability, as measured by lactae dehydrogenase (LDH) leakage, suggesting that menadione might induce cell lysis rather than aggregation of platelets. Turbidty changes induced by menadione were unaffected by addition ofl dicoumarol, which is a quinone reducellular factions of patelets. These data, which indicate an absence of the QR detoxifying pathway, suggest that platelets may be more susceptible to menadione-induced cytotoxicity than certain other cell, as hepatocytes.

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Virucidal efficacy of a disinfectant solution composed of n-alkyl-dimethyl-benzyl-ammonium chloride against porcine epidemic diarrhea virus

  • Cha, Chun-Nam;Yu, Eun-Ah;Yoo, Chang-Yeul;Cho, Ki-Yung;Lee, Soo-Ung;Kim, Suk;Lee, Hu-Jang
    • Korean Journal of Veterinary Service
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    • v.37 no.2
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    • pp.105-110
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    • 2014
  • Porcine epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic diarrhea (PED) and causes a considerable economic loss in swine industry. In this study, the virucidal efficacy of the disinfectant composed to n-alkyl-dimethyl-benzyl-ammonium chloride (n-ADBAC) was investigated against PEDV. A virucidal efficacy was determined with the viability of PEDV contacted with the disinfectant in Vero cells. The disinfectant and PEDV were reacted on the hard water (HW) or organic matter suspension (OM) condition. On HW condition, PEDV was inactivated with 50 fold dilutions of the disinfectant. When the antiviral effect on OM condition was evaluated, the antiviral activity of the disinfectant showed on 10 fold dilutions against PEDV. As the disinfectant possesses the virucidal efficacy against PEDV, the disinfectant solution can be used to limit the spread of animal viral diseases.