• Title/Summary/Keyword: HepG2 2.2.15

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Dihydroartemisinin inhibits HepG2.2.15 proliferation by inducing cellular senescence and autophagy

  • Zou, Jiang;Ma, Qiang;Sun, Ru;Cai, Jiajing;Liao, Hebin;Xu, Lei;Xia, Jingruo;Huang, Guangcheng;Yao, Lihua;Cai, Yan;Zhong, Xiaowu;Guo, Xiaolan
    • BMB Reports
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    • v.52 no.8
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    • pp.520-525
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    • 2019
  • Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, ${\gamma}-H_2AX$, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy.

Inhibitory Effects of Terminalia chebula, Sanguisorba officinalis, Rubus coreanus and Rheum palmatum on Hepatitis B Virus Replication in HepG2 2.2.15 Cells (HepG2 2.2.15 세포주를 이용한 가자, 지유, 복분자, 대황의 B형 간염바이러스 증식 억제 효과)

  • 김태균;박민수;한형미;강석연;정기경;류항묵;김승희
    • YAKHAK HOEJI
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    • v.43 no.4
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    • pp.458-463
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    • 1999
  • This study was undertaken to test for antiviral activity of the aqueous extracts prepared from 4 medicinal plants of Korea (Terminalia chebula, Sanguisorba officinalia, Rubus coreanus, Rheum palmatum). Aqueous extracts were assayed for the inhibition of hepatitis B virus (HBV) replication by measurement of HBV DNA and surface antigen (HBsAg) levels in the extracellular medium of HepG2 2.2.15 cells. All extracts decreased the levels of extracellular HBV virion DNA at concentrations ranging from 64 to $128{\;}\mu\textrm{g}/ml$ and inhibited the production of HBsAg dose-dependently. Among the 4 tested plants, Terminalia chebula exhibits the most prominent anti-HBV activities. Our findings suggest that these 4 medicinal plants may have potential to develop as specific anti-HBV drugs in the future.

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Drug Resistance Effects of Ribosomal Protein L24 Overexpression in Hepatocellular Carcinoma HepG2 Cells

  • Guo, Yong-Li;Kong, Qing-Sheng;Liu, Hong-Sheng;Tan, Wen-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9853-9857
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    • 2014
  • Background: The morbidity and mortality rate of liver cancer continues to rise in China and advanced cases respond poorly to chemotherapy. Ribosomal protein L24 has been reported to be a potential therapeutic target whose depletion or acetylation inhibits polysome assembly and cell growth of cancer. Materials and Methods: Total RNA of cultured amycin-resistant and susceptible HepG2 cells was isolated, and real time quantitative RT-PCR were used to indicate differences between amycin-resistant and susceptible strains of HepG2 cells. Viability assays were used to determine amycin resistance in RPL24 transfected and control vector and null-transfected HepG2 cell lines. Results: The ribosomal protein L24 transcription level was 7.7 times higher in the drug-resistant HepG2 cells as compared to susceptible cells on quantitative RT-PCR analysis. This was associated with enhanced drug resistance as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions: The ribosomal protein L24 gene may have effects on drug resistance mechanisms in hepatocellular carcinoma HepG2 cells.

The Effect of Herbs on Inhibition of HBeAg Production in HepG2.2.15 Cell line (수종의 한약재가 HepG 2.2.15 Cell의 HBeAg발현 억제에 미치는 효과(效果))

  • Woo, Hong-Jung;Lee, Jang-Hoon;Kim, Young-Chul
    • The Journal of Internal Korean Medicine
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    • v.20 no.1
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    • pp.122-132
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    • 1999
  • Purpose : Hepatitis B virus DNA transfected cell line(HepG2.2.15) was cultured to evaluate the effect of herbs on the expression of HBeAg and the replication of HBV. HepG2.2.15 produces HBV particles as well as viral proteins into cell culture media. Methods : Extracts of herbs were adminitered to the cells on the proper concentration. Culture media was collected 48 hours after the herbal administration and HBeAg level in the media was examined by ELISA method. To confirm that the anti-viral effect was not due to direct cytotocixity of the extracts, normal cell proliferation was shown by cell counting. And as of the interference in protein synthesis of HepG2.2.15 by herb-extracts, we used the result of study that we performed before by ${\alpha}FP$ assay using EIA method. Results& Conclusion : Herb medicines like 地楡(Sanguisorbae Radix) and 覆盆子(Rubi Frusctus) showed significant inhibitory effect on HBeAg expression at p<0.01 and 五味子(Acanthopanacis Cortex) at p<0.05. Whereas, though some herbs such as ?草根(Rubiae Radix), 山査(Crataegii Fructus), 白芍藥(Paeoniae Radix Alba), and 大黃(Rhei Radix et Rhizoma) showed the tendecy to suppress HBeAg. most of them were not significant statistically. From the above, we could conclude that those herb medicines can be applied to patients effectively and further studies on effective fraction of some herbs are thought to be needed.

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Antiviral Effect of a Combination Therapy of Amantadine/Biphenyl Dimethyl Dicarboxylate in HepG2 2.2.15 (간암세포주 HepG2 2.2.15에서 아만타딘/비페닐디메칠디카르복실레이트 복합제의 항 바이러스 효과)

  • Joo, Seong-Soo;Won, Tae-Joon;Lee, Yong-Jin;Hwang, Kwang-Woo;Lee, Do-Ik
    • YAKHAK HOEJI
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    • v.49 no.2
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    • pp.151-155
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    • 2005
  • For decades, the demand for new antiviral strategies, especially in hepatitis, has increased markedly due to its devastating pathogenic outcome, In the present study, we examin ed the antiviral effect of the combination of amantadine and biphenyl dimethyl dicarboxylate (DDB) in HepG2 2.2.15, which is transfected with HBV DNA. The study demonstrated that the combination not the single treatment may have an anti-HBV effect through a synergism of antiviral, anti-inflammatory and cytoprotective activities in STAT1 ${\alpha}$, 6-16 gene, and pro-inflammatory components such as nitric oxide and IL-1${\beta}$ expression. In addition, hepatitis B surface and core gene expression were examined as a final end point for the anti-HBV activities, which was also significantly suppressed comparing to normal control (p<0.01).

Analytical Research to Determine the effects of the Components of ONGABO on the Viability of HepG2 Cancer Cells by Using the Sovereign, Minister, Assistant and Courier Principle (君臣佐使論)

  • Shin, Jeong-Hun;Jun, Seung-Lyul;Hwang, Sung-Yeoun;Ahn, Seong-Hun
    • Journal of Pharmacopuncture
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    • v.15 no.4
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    • pp.42-51
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    • 2012
  • Objectives: This study used the basic principle of Oriental medicine, the sovereign, minister, assistant and courier principle (君臣佐使論) to investigate the effects of the component of ONGABO, which is composed of Ginseng Radix (Red Ginseng), Angelica Gigantis Radix, Schisandrae Fructus, Cuscuta Semen and Curcumae tuber on the viability of HepG2 cells. Methods: Single and mixed extracts of the component of ONGABO were prepared by lypohilizing powder of Red Ginseng (6-year root from Kanghwa), Angelica Gigantis Radix, Schisandrae Fructus, Cuscuta Semen, Curcumae Tuber (from Omniherb Co., Ltd., Korea) at the laboratory of herbal medicine in Woosuk University and were eluted after being macerated with 100% ethanol for three days. The cell viability of HepG2 was determined by using an absorptiometric analysis with PrestoBlue (Invitrogen) reagent after the plate had been incubated for 48 hours. All of the experiments were repeated three times to obtain the average value and standard deviation. The statistical analysis was done and the correlation factor was obtained by using Microsoft Office Excel 2007 and Origin 6.0 software. Results: Although Ginseng Radix (Red Ginseng) and Schisandrae Fructus did not enhance the viability of HepG2 cells, they were shown to provide protection of those cells. On the other hand, Angelica Gigantis Radix decreased the viability of HepG2 cells significantly, Cuscuta Semen and Curcumae Tuber had a small or no effect on the viability of HepG2 cells. Conclusions: In the sovereign, minister, assistant and courier principle (君臣佐使論), Ginseng Radix (Red Ginseng) corresponds to the sovereign component because it provides cell protection effects, Angelica Gigantis Radix corresponds to minister medicinal because it kills cells, Schisandrae Fructus corresponds to the assistant medicinal to help red ginseng having cell protect effects. Cuscuta Semen and Curcumae Tuber correspond to the courier medicinal having no effect in cell viability in HepG2. We hope this study provides motivation for advanced research on the sovereign, minister, assistant and courier principle.

Cytotoxicity Assessments of Portulaca oleracea and Petroselinum sativum Seed Extracts on Human Hepatocellular Carcinoma Cells (HepG2)

  • Farshori, Nida Nayyar;Al-Sheddi, Ebtesam Saad;Al-Oqail, Mai Mohammad;Musarrat, Javed;Al-Khedhairy, Abdulaziz Ali;Siddiqui, Maqsood Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6633-6638
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    • 2014
  • The Pharmacological potential, such as antioxidant, anti-inflammatory, and antibacterial activities of Portulaca oleracea (PO) and Petroselinum sativum (PS) extracts are well known. However, the preventive properties against hepatocellular carcinoma cells have not been explored so far. Therefore, the present investigation was designed to study the anticancer activity of seed extracts of PO and PS on the human hepatocellular carcinoma cells (HepG2). The HepG2 cells were exposed with $5-500{\mu}g/ml$ of PO and PS for 24 h. After the exposure, cell viability by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, neutral red uptake (NRU) assay, and cellular morphology by phase contrast inverted microscope were studied. The results showed that PO and PS extracts significantly reduced the cell viability of HepG2 in a concentration dependent manner. The cell viability was recorded to be 67%, 31%, 21%, and 17% at 50, 100, 250, and $500{\mu}g/ml$ of PO, respectively by MTT assay and 91%, 62%, 27%, and 18% at 50, 100, 250, and $500{\mu}g/ml$ of PO, respectively by NRU assay. PS exposed HepG2 cells with $100{\mu}g/ml$ and higher concentrations were also found to be cytotoxic. The decrease in the cell viability at 100, 250, and $500{\mu}g/ml$ of PS was recorded as 70%, 33%, and 15% by MTT assay and 63%, 29%, and 17%, respectively by NRU assay. Results also showed that PO and PS exposed cells reduced the normal morphology and adhesion capacity of HepG2 cells. HepG2 cells exposed with $50{\mu}g/ml$ and higher concentrations of PO and PS lost their typical morphology, become smaller in size, and appeared in rounded bodies. Our results demonstrated preliminary screening of anticancer activity of Portulaca oleracea and Petroselinum sativum extracts against HepG2 cells, which can be further used for the development of a potential therapeutic anticancer agent.

cDNA Sequences for Asialoglycoprotein Receptor from Human Fetal Liver

  • Lee, Dong-Gun;Lee, Sung-Gu;Kim, Kil-Lyong;Hahm, Kyung-Soo
    • BMB Reports
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    • v.30 no.4
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    • pp.299-301
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    • 1997
  • The asialoglycoprotein receptor (ASGPR) was the first described mammalian lectin that mediates the specific binding and internalization of galactose/N-acetylgalactosamine-terminating glycoproteins by hepatic parenchymal cells. H1 and H2 are known as essential subunits of the functional ASGPR. There were close similarities in ASGPR H2 subunits between cultured cell line HepG2 and normal human liver cells including identical sequences at both termini. It was therefore expected that there may be some similarities between the subunits from normal liver cells and fetal liver cells. The two subunits of human fetal liver ASGPR. designated FL-H1 and FL-H2. were cloned from cDNA library by peR and the sequences were compared with the known HI and H2 sequences of HepG2, and the H1 sequence of nornal human liver cells. The results showed that FL-H1 was identical to H1 of HepG2. Whereas FL-H2 contains a 15-bp miniexon, but missing 57-bp at the near upstream from the membrane-spanning domain compared to H2 of HepG2 and normal human liver cells indicating that FL-H2 resulted from a differential splicing compared to HepG2 and normal liver cells.

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The Effects of Pomegranate Extracts on the Growth Inhibition against HepG-2 Liver Cancer Cells and Antioxidant Activities (석류 추출물의 간암세포 성장 억제 및 항산화 활성 효과)

  • Park, Kyong-Tae;Kim, Du-Woon;Sin, Tae-Sun;Shim, Sun-Yup;Kim, Mun-Yong;Chun, Soon-Sil
    • Culinary science and hospitality research
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    • v.15 no.1
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    • pp.120-127
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    • 2009
  • In this study, Pip(Pip) and shell powder(Cortex) extracts, and juice concentrates(Juice-1 and Juice-2) of Pomegranate were screened for their growth inhibition on HepG-2 cells and antioxidant activities on DPPH radical-scavenging activity. All samples with higher concentrations showed the growth inhibition against HepG-2 cells. The growth inhibitions against HepG-2 liver cancer cells at 2,500 ppm were in order of Juice-2(43%), Pip(42%), Cortex(38%) and Juice-1(29%). DPPH radical-scavenging activities were higher with the concentrations of the samples increased. The activities of antioxidant BHT, Pip, Cortex, Juice-1, and Juice-2 at 12.5 ppm were 29.9, 16.2, 60.8, 12.6, and 15.1% respectively and those at 25, 50, 100, and 200 ppm were in order of Cortex(81.9$\sim$85.3%), Pip(33.4$\sim$83.0%), BHT(31.3$\sim$47.8%), Juice-2(15.4$\sim$36.8%) and Juice-1(13.4$\sim$36.1%).

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포공영(蒲公英) 분획(分劃)의 간암세포(肝癌細胞)에 대(對)한 항암활성(抗癌活性)과 항암제(抗癌劑)와의 병용투여효과(倂用投與效果)

  • Kim, Dong-Hui;Kim, Seong-Hun
    • The Journal of Korean Medicine
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    • v.16 no.2 s.30
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    • pp.386-413
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    • 1995
  • In order to prove the antitumor effect of Taraxaci Herba experimentally, studies were done. The antitumor effect against hepatic cancers such as Hep G2. Hep 3B & PLC and also the synergstric action was evaluated in the combined treatment with anticancer drugs using chiefly for liver cancer. such as. The results were obtained as follows: 1.$IC_{50}$ against Hep G2. Hep 3B and PLC was $15.5{\mu}g/ml.\;25.4{\mu}g/ml,\;31.25{\mu}g/ml$ in Mitomycin C(MMC), $92.5{mu}g/ml,\;50.2{\mu}g/ml,\;62.5{\mu}g/ml $in cisplatin(CPT) and 125 in 5-flurouracil(5-FU) respectively. 2. In cytotoxic effect against Hep G2 every fractions showed the anti tumor effect as compared with the data of control but EE fraction of Taraxaci Herba was most effective and also hexane fraction was most effective in the combined treatment with anticancer drugs. 3. In cytotoxic effect against Hep 3B every fractions showed the antitumor effect as compared with the data of control but EE fraction of Taraxaci Herba was most effective and also hexane fraction was most effective in the combined treatment with anticancer drugs. 4. In cytotoxic effect against PLC every fractions showed the anti tumor effect in the concentrations of $10^{-5}g/ml$ above as compared with the data of control and also the combined treatment with MMC was most effective. 5. Fractions of Taraxaci Herba showed the most antitumor effect against Hep 3B and also the combined treatment with MMC was most effective. From the above result it was concluded that ethyl ether fraction of Taraxaci Herba was most effective fraction, every fraction showed more antitumor effect against Hep 3B and Hep G2 than PLC.

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