• Title/Summary/Keyword: Physiological mechanism of Death

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Antiproliferative Effect and Apoptotic Mechanism of Extract of Corydalis Yanhusuo on Human Hepatocarcinoma Cells (현호색(玄胡索)이 인체간암세포 증식억제 및 apoptosis 유발에 미치는 영향)

  • Oh, Myun- Taek;Eom, Hyun-Sup;Chi, Gyoo-Yong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.6
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    • pp.1437-1449
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    • 2007
  • In this study, the effect of extract of Corydalis yanhusuo (ECT) used in Oriental medicine therapy was investigated on the cell growth and apoptosis of HepG2 human hepatoma cells. It was found that ECT could inhibit the cell growth effectively in a dose-dependent manner, which was associated with morphological change and apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. And we observed the effects of ECT on loss of mitochondrial membrane potential (MMP), using the JC-1 probe by DNA flow cytometric analysis. Apoptosis of HepG2 cells by ECT was associated with a down-regulation of anti apoptotic Bcl-2 expression, inhibitor of apoptosis proteins (IAPs) expression and proteolytic activation of caspase-3 and caspase-9. However, ECT did not affect the pro-apoptotic Bax expression and activity of caspase-8. ECT treatment also concomitant degradation and /or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$). Furthermore, ECT treatment caused a dose-dependent inhibition of iNOS and cyclooxygenase-2 (Cox-2). Additionally ECT have been implicated in the regulation of telomerase expression. ECT treatment induced the down-regulation of telomerase reverse transcriptase mRNA (hTERT) expression of HepG2 cells. Taken together, these findings suggest that ECT may be a potential chemotherapeutic agent for the control of HepG2 human hepatoma cells.

Effects of Dancheonhwan on Hydrogen Peroxide-induced Apoptosis of H9c2 Cardiomyoblasts (단천환이 Hydrogen Peroxide에 의한 심근세포 독성에 미치는 영향)

  • Na Yeong Hun;Bak Sang Beom;Jeong Seung Won;Yun Jong Min;Lee In;Moon Byung Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.3
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    • pp.774-782
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    • 2004
  • The water extract of Dancheonhwan (DCH) has been used to treat ischemic brain and heart damage in oriental medicine. However, little is known about the mechanism by which the water extract of DCH rescues cells from ischemic damage. Therefore, this study was designed to investigate the protective mechanisms of DCH on the H₂O₂-induced toxicity in H9c2 cardiomyoblast cells. Treatment of H₂O₂ markedly decreased the viability of H9c2 cardiomyoblast in a dose-dependent and time-dependent manner. The nature of H₂O₂-induced toxicity of H9c2 cells resulted from apoptotic death confirmed with genomic DNA fragmentation. DCH increased the viability of H₂O₂-treated H9c2 cells by about 23%, and partially suppressed the genomic DNA fragmentation and PARP cleavage. H₂O₂ also activated caspase-3 protease and -9 protease, but not both caspase-6 protease and -8 protease. H₂O₂ induced the mitochondria dysfunction, including mitochondria membrane permeability transition (MPT) and cytosolic release of cytochrome c from mitochondria, which was prevented in part by pretreatment of DCH. N-acetylcystein (NAC), a free-radical scavenger, alone increased the viability of H₂O₂-treated H9c2 cells in a dose-dependent manner. Furthermore, the combination of NAC with DCH significantly increased the viability of the H₂O₂-treated H9c2 cells in a dose-dependent manner. These data indicate that DCH has the protective effect on ROS-induced apoptosis of cadiomyoblast H9c2 cells.

Protective Effect of Radix Clematidis Extract on Streptozotocin-induced Diabetes (Streptozotocin 유도 당뇨병에 대한 위령선(威靈仙) 추출물의 방어 효과)

  • Ham, Kyung-Wan;Kim, Eun-Kyung;Song, Mi-Young;Kwon, Kang-Beom;Song, Je-Ho;Seo, Eun-A;Ryu, Do-Gon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.3
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    • pp.580-584
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    • 2008
  • In the present study, Radix clematidis extract (RCE) was evaluated to determine if it could protect pancreatic ${\beta}$ cells against multiple low dose streptozotocin (MLDS)-induced diabetes. Injection of mice with MLDS resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining. However, the induction of diabetes by MLDS was completely prevented when mice were pre-administrated with RCE. Generation of oxidative stress is implicated in MLDS, a ${\beta}$ cell specific toxin-induced islet cell death. In this context, to elucidate the mechanisms of protective effects in RCE pre-administrated diabetic mice, we investigated the expression of heme oxygenase-1 (HO-1), which is one of the anti-oxidant enzymes. MLDS-induced HO-1 expressions were significantly reduced in MLDS-treated mice. However, the decrease of HO-1 by MLDS were protected by pretreatment of RCE. The molecular mechanism by which RCE inhibits diabetic conditions by MLDS appears to involve inhibition of HO-1 expression. Taken together, these results reveal the possible therapeutic value of RCE for the prevention of type 1 diabetes progression.

Protective Effect of Pueraria Radix Extract on the Cisplatin-induced Cytotoxicity of HEI-OC1 Cells Via Scavenging of Free Radicals (갈근 추출물이 Cisplatin으로 손상된 HEI-OC1 청각세포보호와 유리라디칼 소거능에 미치는 영향)

  • Yu, Hyeon-Hee;Seo, Se-Jeong;Moon, Hae-Dalma;Park, Rae-Kil;So, Hong-Seob;Jeon, Byung-Hun;Jung, Su-Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.2
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    • pp.462-467
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    • 2007
  • The radix of Pueraria thunbergiana BENTHAM (Leguminosae) is traditionally prescribed to attenuate the clinical manifestations of inner ear dysfunction and various clinical situations including fever, gastrointestinal disorders, skin problems, migraine headaches, lowering cholesterol and treating chronic alcoholism in Oriental Medicine. In the present study, we examined the effect of ethanol extract of P. thunbergiana radix (EPR) on cisplatin-mediated HEI-OC1 auditory cell death. In addition, to investingate the protection mechanism of EPR on free radicals. Treatment of EPR protected cells from cisplatin and reduced lipid peroxidation in a dose-dependent manner. Furthermore, EPR demonstrated significant scavenging activity against various free radicals, including superoxide radical, hydroxyl radical, hydrogen peroxide, and DPPH radical. These results indicate that EPR protects cisplatin-induced damages of HEI-OC1 cells through inhibition of lipid peroxidation and augmenting scavenging activities against free radials.

Danchunhwan Protects the Cytotoxicity of Beta-amyloid in SH-SY5Y Neuroblastoma Cells (베타아밀로이드 유도성 SH-SY5Y 세포독성에서 단천환(丹川丸)의 보호효과)

  • Yu, Bong-Sun;Kim, Jin-Kyung;;Park, Chan-Ny;So, Hong-Seob
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1516-1523
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    • 2006
  • The water extract of Danchunhwan(DCH) has been traditionally used for treatment of dementia damage in oriental medicine. However, little is known about the mechanism by which the water extract of DCH rescues cells from neurodegenerative disease such as Alzheimer's disease. This study was designed to investigate the protective mechanisms of DCH on ${\beta}$-amyloid or $H_2O_2$-induced cytotoxicity in SH-SY5Y neuronblastoma cells. ${\beta}$-amyloid and $H_2O_2$ markedly decreased the viability of SH-SY5Y cells, which was characterized with apparent apoptotic features such as membrane blebbing as well as fragmentation of genomic DNA and nuclei. However, the water extract of DCH significantly reduced both ${\beta}$-amyloid or $H_2O_2$-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Also, the water extract of DCH prevented prevented the mitochondrial dysfunction including the disruption of mitochondria membrane permeability transition (MPT) and the perturbation in Bcl-2 family protein expressions in $H_2O_2$-treated SH-SY5Y cells.

Apoptosis-inducing Effect of Fructus Trichosanthis in HL-60 Leukemic Cells (백혈병 세포주 HL-60에서 과루실 세포고사 유도 효과)

  • Kwon Kang Beom;Kim Eun Kyung;Han Mi Jeong;Ryu Do Gon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.903-907
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    • 2005
  • Many naturally occurring plant extracts are studied for their beneficial effects for health and particularly on cancer. Apoptosis, or programmed cell death, occurs in both normal and pathological conditions, including cancer Dysregulation of apoptosis allows transformed cells to continually and uninhibitedly enter the cell cycle, thus perpetuating the sequence of mutation, genomic instability and, finally, oncogenesis. To investigate the apoptosis-inducing effect of the extract of Fructus Trichosanthis (EFT) on leukemic HL-60 cells and its mechanism, HL-60 cells in vitro in culture medium were given different doses of the extract. The inhibitory rate of cells were measured by microculture tetrazolium assay, cell apoptotic rate was detected by flow cytometry, morphology of cell apoptosis was observed by DAPI fluorescence staining, and the activations of caspases and PARP were detected using Western blotting analysis. The extract could activate the caspase-3 and caspase-8, induce PARP cleavage, inhibit growth of HL-60 cells, and cause apoptosis significantly The suppression was in dose-dependent manner. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly by DAPI fluorescence staining especially. These results will provide strong laboratory evidence of EFT for clinical treatment of acute leukemia.

Effects of the Bee Venom on Human Gastric Adenocarcinoma Cell Lines (봉독이 위암 세포주에 미치는 효과)

  • Heo, Gyeong;Kim, Myung Ho;Lim, Seong Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.1
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    • pp.92-98
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    • 2013
  • Bee Venom(below BV) has been used in alternative medicine to treat the diseases, such as pain diseases. BV contains a variety of peptides, including melittin, apamin, adolapin, MCD peptide, enzymes(i.e. PLA2), amines(i.e. histamine and epinephrine), and nonpeptide components. The two main components of BV are melittin and PLA2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the depress of cancer cell. Melittin and PLA2 have been reported to induce apoptosis and to possess anti-cancer effects and neurite outgrowth in PC12 cells. Analysis of proliferation was confirmed by MTT assay. BV decreased cell number through dose- and duration-dependent manner and these effects are apparent at a concentration of 3 ${\mu}g/ml$. To observe which signaling molecules will be activated by BV, phosphorylation of ERK, p38 MAPK, JNK and ERM were examined by Western blot analysis. To study the long term effect of BV in human gastric adenocarcinoma cell lines, the image of cells treated with BV for 4 days were obtained. BV was shown to exhibit anti-cancer activity in human gastric adenocarcinoma cell lines at a broad range of concentrations of 3 ${\mu}g/ml$. ERK, p38 MAPK and JNK were found to increase in BV treated cells. However, ERM which known to be involved in the cell death, was gradually decreased to 30minutes after addition 3 ${\mu}g/ml$ of BV. These results provide a possible BV-induced inhibitory signal for cancer proliferation that is initiated by the decrease in ERM activity. Moreover, it is likely that the activation of ERK, p38 MAPK and JNK are required for the BV-induced inhibition of cancer proliferation.

Induction of apoptosis by methanol extracts of Ficus carica L. in FaDu human hypopharynx squamous carcinoma cells

  • Lee, Seul Ah;Park, Bo-Ram;Kim, Chun Sung
    • International Journal of Oral Biology
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    • v.45 no.3
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    • pp.99-106
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    • 2020
  • Ficus carica L. (fig) is one of the first cultivated crops and is as old as humans. This plant has been extensively used as a traditional medicine for treating diseases, such as cough, indigestion, nutritional anemia, and tuberculosis. However, the physiological activity of fig leaves on oral cancer is as yet unknown. In this study, we investigated the anticancer effect of methanol extracts of Ficus carica (MeFC) and the mechanism of cell death in human FaDu hypopharyngeal squamous carcinoma cells. MeFC decreased the viability of oral cancer (FaDu) cells but did not affect the viability of normal (L929) cells, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay and Live and Dead assay. In addition, MeFC induced apoptosis through the proteolytic cleavage of procaspase-3, -9, poly (ADP-ribose) polymerase (PARP), downregulation of Bcl-2, and upregulation of Bax, as determined by 4′,6-diamidino-2-phenylindole dihydrochloride staining and western blot analysis. Moreover, a concentration of MeFC without cytotoxicity (0.25 mg/mL) significantly suppressed colony formation, a hallmark of cancer development, and completely inhibited the colony formation at 1 mg/mL. Collectively, these results suggest that MeFC exhibits a potent anticancer effect by suppressing the growth of oral cancer cells and colony formation via caspase- and mitochondrial-dependent apoptotic pathways in FaDu human hypopharyngeal squamous carcinoma cells. Therefore, the methanol extract of Ficus carcica leaves provide a natural chemotherapeutic drug for human oral cancer.

Chitosan Increases the Release of Renal Dipeptidase from Porcine Renal Proximal Tubule Cells

  • Hyun Joong, Yoon;Kim, Young-Ho;Park, Sung-Wook;Lee, Hwanghee-Blaise;Park, Haeng-Soon
    • Animal cells and systems
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    • v.7 no.4
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    • pp.309-315
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    • 2003
  • Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) has been widely studied since it was first purified from porcine kidney brush border membrane. It was reported that RDPase activity in urine samples of acute and chronic renal failure patients decreases. Nitric oxide (NO) is a highly reactive free radical involved in a number of physiological and pathological processes. NO is able to act in a dual mode, leading either to induction of apoptosis or to blunted execution of programmed cell death. NO inhibited the RDPase release from porcine renal proximal tubules, which could be blocked by L-NAME. Chitosan, the linear polymer of D-glucosamine in $\beta$(1\longrightarrow4) linkage, not only reversed the decreased RDPase release by NO but also increased NO production in the proximal tubule cells. The stimulatory effect of NO on RDPase release from proximal tubules in the presence of chitosan must be different from the previously proposed mechanism of RDPase release via NO signaling pathway. Chitosan stimulated the RDPase release in the proximal tubules and increased RDPase activity to 220% and 250% at 0.1% and 1%, respectively. RDPase release was decreased to about 40% in the injured proximal tubules and was recovered in proportion to the increase of chitosan. Chitosan may be useful in recovery of renal function from $HgCl_2$injury.

Effect of Ethanol Extracts of Raw and Boiled Bracken on Blood Pressure in Cats (고사리 (Pteridium aquilinum) Ethanol 추출액(抽出液)에 의한 혈압강하작용(血壓降下作用))

  • Koh, Sang-Don;Kim, Kee-Soon
    • The Korean Journal of Physiology
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    • v.18 no.2
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    • pp.171-180
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    • 1984
  • The death of cattle from acute bracken poisoning has been recognized for many years. Acute bracken poisoning is characterized by mucoidal nasal and anal hemorrhage, severe anorexia. pyrexia, gastric ulcer and myocardial damage. In 1958 Evans first suggested that clinical picture of bracken poisoning was very much similar to that of radiation injuries such as aplastic anemia, leucopenia, thrombocytopenia and increased capillary fragility. Bracken has been clearly demonstrated to contain a carcinogen as well as thiaminase. However, the nature of carcinogen in bracken has not definetely elucidated. Also it was warned by several workers that bracken could be a causative factor for stomach cancer in Korean and Japanese. It appears that little is known on the e(feet of bracken on the function of cardiovascular system. Therefore the present study was designed to explore effects of ethanol extract of raw and toiled bracken (RBEE:BBEE) on blood pressure in cats. Also studied was the mechanism underlying changed in blood pressure of cats by bracken. The result obtained were as follows; 1) Mean arterial blood pressure was invariably decreased following administration of either RBEE or BBEE. Tn general depressor responses to RBEE persisted longer than that to BBEE. Generally, depressor responses were proportional to debases of RBEE and BBEE administered. 2) After administration of 60 mg/kg RBEB and BBEE, blood Pressure decreased by $62.1{\pm}1.7mmHg$ and $68.0{\pm}3.0mmHg$, respectively. No change was observed between depressor responses to RBEE and that to BBEE. 3) Depressor responses to BBEE and RBEE were not affected by vagotomy, propranolol and regitine. 4) In atropinized animal depressor responses to BBEE and RBEE were reduced by 30-40% showing part of depressor response was resulted from cholinergic effect of bracken.

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