• 제목/요약/키워드: DNA Synthesis Inhibition

검색결과 109건 처리시간 0.023초

放射線을 照射한 흰쥐의 여러 가지 組織내의 DNA의 合成과 分解 (Postirradiation Synthesis and Degradation of DNA in Various Tissues of Rats)

  • Kang, Man-Sik
    • 한국동물학회지
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    • 제14권4호
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    • pp.199-204
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    • 1971
  • 放射線照射에 의해서 尿 및 血液內에 다량의 deoxycytidine (CdR)이 流出하는 것을 볼수가 있는데, 이것이 DNA의 合成이나 分解와 어떤 관련성이 있으며, 아울러 어느 臟器의 DNA가 放射線感受性이 큰지의 여부를 밝히기 위해서 400R의 X 線을 흰쥐에 全身照射시켜, 간, 지라 및 흉선을 切除하여 均質化시킨 후, CdR-2-$^14 C$을 써서 DNA의 合成率 및 分解率을 測定하였다. DNA의 合成率은 흉선의 경우, 照射후 1 $\\sim$ 3日에 가장 심한 抑制現象이 나타났으며 5日후 부터는 점차 回復됨을 볼 수 있었고, 한편 간과 지라의 경우는 抑制의 정도가 흉선에 비해서 적었으며 回復도 훨씬 빨리 이루어졌다. DNA의 分解率은 지라와 흉선의 경우 비슷하여서 照射후 1日에 영향이 極大로 나타냈으며 回復도 아주 늦게 일어남을 볼 수 있었는데 반해서, 간의 경우는 分解도 덜 일어났으며 回復도 아주 빨리 일어남을 알 수 있었다. 이와 같은 결과는 각종 臟器의 放射線感受性의 차와 再生能의 차에 의해서 나타나는 현상임을 알 수 있고 CdR의 流出量의 增加는 放射線에 의한 DNA合成의 抑制와 DNA分解의 促進의 두가지 요인에 기인하는 것으로 추정되었으며, 전자의 경우는 흉선이, 후자의 경우는 지라와 흉선이 같은 정도의 重要性을 지니고 있음을 알 수 있었다.

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흰쥐 배양 전배자 및 중뇌세포에서 Ochratoxin A의 독성 (Embryotoxicity of Ochratoxin A in Cultured Rat Embryonic Midbrain Cells and Whole Embryos)

  • 홍진태;박귀례;한순영;박기숙;김형식;오세동;박희정;이이다;장성재
    • 약학회지
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    • 제42권3호
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    • pp.336-344
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    • 1998
  • Effects of ochratoxin A (OTA) on embryo development were studied in cultured whole embryos from 9.5 day gestation rat for 48 h. OTA (more than $0.5{\mu}g/ml$) induced microcephaly in the cultured rat whole embryos. Protein and DNA content, and DNA synthesis were significantly inhibited by OTA. We next examined whether the microcephaly seen in cultured whole embryo partially results from inhibition of differentiation of embryonic midbrain cells. Embryonic midbrain cells were extracted from 12 day gestation rat embryos, and cultured for 96 hr. OTA ibhibited cell differentiation about 50% over control. We also tested whether OTA-induced embryotoxicity would be associated with oxidative damages. We measured the ${\gamma}$-glutamyltranspeptidase (${\gamma}$-GT) and glutathione peroxidase (GPX) activities, and glutathione (GSH) content in both cultured whole embryos and embryonic midbrain cells. OTA decreased GSH content, whereas slightly increased ${\gamma}$-GT activity, but GPX activity was not significantly changed. These results show that OTA caused the microcephaly and its effect may be partially due to the inhibition of cell differentiation of embryonic midbrain cells, but the role of oxidative damages is not clear in embryotoxicity.

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Anticancer Potential of an Ethanol Extract of Saussurea Involucrata against Hepatic Cancer Cells in vitro

  • Byambaragchaa, Munkhzaya;Cruz, Joseph Dela;Kh, Altantsetseg;Hwang, Seong-Gu
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권18호
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    • pp.7527-7532
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    • 2014
  • Saussurea involucrata is a Mongolian medicinal plant well known for its effects in promoting blood circulation, and anti-inflammation and analgesic functions. Earlier studies reported that Saussurea involucrata has anticancer activity. The purpose of this study was to confirm the anticancer activity of an ethanol extract of Saussurea involucrata against hepatic cancer and elucidate its mechanisms of action. Hepatocellular carcinoma cells were tested in vitro for cytotoxicity, AO/EB staining for apoptotic cells, apoptotic DNA fragmentation and cell cycle distribution in response to Saussurea involucrata extract (SIE). The mRNA expression of caspase-3,-9 and Cdk2 and protein expression of caspase-3,-9, PARP, XIAP, Cdk2 and p21 were analyzed through real time PCR and Western blotting. Treatment with SIE inhibited HepG2 cell proliferation dose- and time-dependently, but SIE only exerted a modest cytotoxic effect on a viability of Chang human liver cells. Cells exposed to SIE showed typical hallmarks of apoptotic cell death. Cell cycle analysis revealed that SIE caused G1-phase arrest in HepG2 cells. In conclusion, Saussurea involucrata ethanol extract has potential cytotoxic and apoptotic effects on human hepatocellular carcinoma cells. Its mechanism of action might be associated with the inhibition of DNA synthesis, cell cycle (G1) arrest and apoptosis induction through up-regulation of the protein expressions of caspase-3,-9 a nd p21, degradation of PARP and down-regulation of the protein expression of Cdk2 and XIAP.

Lisophosphatidic Acid Inhibits Melanocyte Proliferation via Cell Cycle Arrest

  • Kim, Dong-Seok;Park, Seo-Hyoung;Kim, Sung-Eun;Kwon, Sun-Bang;Park, Eun-Sang;Youn, Sang-Woong;Park, Kyoung-Chan
    • Archives of Pharmacal Research
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    • 제26권12호
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    • pp.1055-1060
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    • 2003
  • Lysophosphatidic acid (LPA) is a well-known mitogen in various cell types. However, we found that LPA inhibits melanocyte proliferation. Thus, we further investigated the possible signaling pathways involved in melanocyte growth inhibition. We first examined the regulation of the three major subfamilies of mitogen-activated protein (MAP) kinases and of the Akt pathway by LPA. The activations of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) were observed in concert with the inhibition of melanocyte proliferation by LPA, whereas p38 MAP kinase and Akt were not influenced by LPA. However, the specific inhibition of the ERK or JNK pathways by PD98059 or D-JNKI1, respectively, did not restore the antiproliferative effect. We next examined changes in the expression of cell cycle related proteins. LPA decreased cyclin $D_1 and cyclin D_2$ levels but increased $p21^{WAF1/CIP1}$ (p21) and $p27^{KIP1}$ (p27) levels, which are known inhibitors of cyclin-dependent kinase. Flow cytometric analysis showed the inhibition of DNA synthesis by a reduction in the S phase and an increase in the $G_0/G_1$ phase of the cell cycle. Our results suggest that LPA induces cell cycle arrest by regulating the expressions of cell cycle related proteins.

Helicobacter pylori 감염에 의한 Cytokines 유전자 발현에 대한 치양탕(治瘍湯)의 효과 (Effects of Chiyangtang on Helicobacter pylori-induced increase of cytokines gene expression)

  • 이형주;원진희;문구;문석재;박동원
    • 대한한방내과학회지
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    • 제20권1호
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    • pp.99-110
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    • 1999
  • Effects of Chiyangtang(CYT) on H. pylori-induced increase of interleukin 8 and interleukin 1 gene expression was studied in Kato Ⅲ cell line, a human stomach epithelial cell line. Treatment of H. pylori to the cell culture signifant!y increased IL-8 and IL-1 mRNA synthesis. When CYT was added along with H. pylori, the increase of IL-8 and IL-1 mRNA synthesis was blocked. Activation of transcription factor $NF-{\kappa}B$ and AP-1 which were known to important in IL-8 and IL-1 gene expression was also studied using chloramphenicol acetyltransferase(CAT) assay. Treatment of H. pylori increased activation of $NF-{\kappa}B$ and AP-l and CYT effectively protected the activation. Electrophoretic mobility shift assay suggested that CYT effectively inhibited DNA binding of $NF-{\kappa}B$ and AP-l to their cognate site. These results suggested that CYT could prevent stomach diseases through the down regulation of IL -8 and IL-l gene expression which might be mediated by the inhibition of $NF-{\kappa}B$ and AP-1 activities and their binding to DNA.

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사람 전립선암세포주인 LNCaP에서 셀레늄의 G1/S 세포주기억제에 관한 연구 (Selenium arrest G1/S phase of cell cycle in LNCaP human prostate cancer cells)

  • 남정석;정지윤
    • 한국식품위생안전성학회지
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    • 제24권3호
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    • pp.267-272
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    • 2009
  • 우리 몸에 필수적인 미량원소인 셀레늄은 항암활성이 있는 것으로 알려져 있고, 역학적, 생태학적 그리고 임상시험을 종합해보면, 셀레늄은 종양, 특히 전립선암, 폐암, 대장암에 대한 위험성을 낮출 수 있을 것으로 생각되어진다. 기전연구에 따르면 셀레늄은 DNA single strand breaks와 활성산소종을 유도함으로써 종양을 억제하는 예방효능이 있는 것으로 밝혀지고 있다. 하지만, 아직까지 전립선암세포주에서 methylseloenol 대사체 중에 하나인 MSeA와 세포주기억제와의 관계에 대해서는 명확하게 밝혀져 있지 않은 실정이다. 따라서, 이번 연구에서는 전립선암세포주에서 셀레늄의 세포주기에 관한 효능을 확인해 보고자 하였다. 결과를 종합해보면, MSeA는 전립선암세포주에서 G1/S기 세포주기를 억제하고 DNA 합성을 방해하는 것으로 나타났고, 이러한 현상은 cyclin의존성 키나아제를 길항하는 단백질 중에 하나인 p27단백질의 발현을 증가시킴으로써 일어남을 확인하였다. 따라서, MSeA에 의해 유발되는 세포주기 억제가 전립선암 세포의 성장억제에 기여하는 것으로 사료된다.

F9 기형암종세포에서 Ursolic acid의 apoptosis 유도기작 (Induction of Apoptosis by Ursolic Acid in F9 Teratocarcinoma Cells)

  • 강창모;백진현;김규원
    • 생명과학회지
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    • 제8권1호
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    • pp.51-59
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    • 1998
  • Ursolic acid(UA)의 apoptosis 유도능을 F9 생쥐 기형암종세포를 대상으로 조사하였다. UA는 피부암화의 억제, tumor의 분화유도, tumor promotion의 억제 등의 항암 효과를 나타내는 pentacyclic triterpene acid로 물질로 알려져 있다. UA를 F9세포에 처리하였을 때 농도비례로 성장억제를 나타냈다. 또한 apoptosis과정에서 관찰되는 전형적인 DNA 분절을 관찰할 수 있었고, 전자현미경을 이용한 세포의 미세구조를 관찰한 결과, 역시 apoptosis과정에서 관찰되는 전형적인 형태인 염색질 응축, 핵의 분절들을 관찰할 수 있어, UA에 의한 항암 효과는 apoptosis에 의한 것임을 시사한다. UA에 의한 apoptosis는 단백질 합성저해제인 cycloheximide에 의해 저해됨을 관찰할 수 있었다. UA를 F4쎄포에 처리한 후 oncogene의 발현양상을 조사한 결과, c-myc과 laminin B1은 apoptosis과정동안 점점 감소하고 c-jun은 증가함을 관찰할 수 있었다. 이상의 결과로서 UA에 의한 F9 세포의 apoptosis에는 새로운 단백질의 합성이 요구되며, c-myc 및 laminin의 발현 감소와 c-jumd의 발현 증가가 관여하고 있음을 시사한다.

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산화적 스트레스에 의한 간세포의 DNA 손상 및 apoptosis 유도에 대한 노근 추출물의 보호 효과 (Protective Effect of Phragmitis Rhizoma against Oxidative Stress-induced DNA Damage and Apoptosis in Chang Liver Cells)

  • 이희영;홍상훈;박상은
    • 대한한방내과학회지
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    • 제42권6호
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    • pp.1269-1284
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    • 2021
  • Objectives: Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis Trin., which has been prescribed in traditional Korean medicine to relieve fever and vomiting and to nourish the body fluids. Recently, the protective effect of Phragmitis Rhizoma extract or its components on myelotoxicity and inflammatory responses have been reported, but no study has yet been conducted on oxidative stress. Methods: The present study investigated whether an ethanol extract of Phragmitis Rhizoma (PR) could protect against cellular damage induced by oxidative stress in Chang liver cells. Results: Pretreatment with PR significantly suppressed the hydrogen peroxide (H2O2)-induced reduction of Chang cell viability and generation of reactive oxygen species (ROS), thereby deferring apoptosis. PR also markedly inhibited H2O2-induced comet tail formation and phospho-γH2AX expression, suggesting that PR protected against oxidative stress-mediated DNA damage. PR also effectively prevented the inhibition of ATP synthesis in H2O2-treated Chang cells by inhibiting the loss of mitochondrial membrane potential, indicating that PR maintains energy metabolism through preservation of mitochondrial function while eliminating ROS generated by H2O2. Immunoblotting results indicated that PR attenuated the H2O2-induced downregulation of Bcl-2 and upregulation of Bax expression. Conclusions: PR protects against oxidative injury in Chang liver cells by regulating energy homeostasis via ROS generation blockade, which is at least partly mediated through inactivation of the mitochondria-mediated apoptosis pathway.

들깻잎에서 동정된 Phytol과 Eicosatrienoic Acid의 암세포 증식억제 효과 (Anticancer Activity of Phytol and Eicosatrienoic Acid Identified from Perilla Leaves)

  • 박건영;이경임;이숙희
    • 한국식품영양과학회지
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    • 제28권5호
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    • pp.1107-1112
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    • 1999
  • We investigated the inhibitory effects of phytol and methyl 11,14,17 eicosatrienoic acid (methyl ETA, n 3, 20 : 3) separated from perilla leaves on the growth of human cancer cells. Phytol inhibited significantly the growth of HT 29 human colon cancer cells, MG 63 osteosarcoma cells and AZ 521 gastric cancer cells. Although the activity of methyl ETA was lower than that of phytol, it was also observed to have the inhibitory effect on three human cancer cell lines. Furthermore, the DNA synthesis of the MG 63 osteosarcoma cells was markedly decreased by the addition of the phytol and methyl ETA. These results suggest that phytol and methyl ETA identified from the perilla leaves may play a role on the growth inhibition of the human cancer cells.

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