• Title/Summary/Keyword: HepG2 2.2.15

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Studies on Antitumor Effect and Synergistic Action of Natural Products with Anticancer drugs against Hepatic Tumors (생약의 간암세포에 대한 항종양효과와 항암제와의 상승작용)

  • Park, Gyeong-Sik;kim, Sung-Hoon;kim, Byung-tak
    • Journal of Haehwa Medicine
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    • v.4 no.1
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    • pp.211-223
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    • 1995
  • The antitumor effect of 柴胡(Bupleuri Radix : BP), 茵陳(Artemisiae capillaris Herba; ACH) 및 蒲公英(Taraxaci Herba; TH) and 蒲公英 EE層(Ethyl ether layer of TH; EETH) on human hepatocytes such as Hep G2, PLC and Hep 3B, and synergistic action with the anticancer drugs, that is, mitomycin(MMC), cisplatin(CPT) and 5-fluorouracil(5-FU) were studied by the method of MTT. The results were obtained as follows: 1. $IC_{50}$ against Hep G2, PLC and Hep 3B was $15.5{\mu}g/ml$, $25.4{\mu}g/ml$ and 31.25 in MMC, $92.5{\mu}g/ml$, $50.2{\mu}g/ml$ and $62.5{\mu}g/ml$ in CPT and $125{\mu}g/ml$ in 5-FU respectively. 2. Cytotoxic effect on Hep G2 was obvious in BP-treated group, synergistic action was most effective in TH-treated group or with MMC. 3. Cytotoxic effect on Hep 3B was obvious in ACH-treated group, synergistic action was most effective in ACH-treated group or with MMC. 4. Cytotoxic effect on PLC was obvious in ACH-treated group, synergistic action was most effective in TH-treated group or with MMC. From above results it was concluded that ACH showed the best antitumor effect against PLC and Hep 3B, BP aganst Hep G2 and also synergistic effect was most effective with MMC, which indicates that it is necessary to seperate the antitumor substances in ACH.

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EGF Reverses Multi-drug Resistance via the p-ERK Pathway in HepG2/ADM and SMMC7721/ADM Hepatocellular Carcinoma Models

  • Yan, Feng;Bai, Li-Ping;Gao, Hua;Zhu, Chang-Ming;Lin, Li;Kang, Xiang-Peng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2619-2623
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    • 2014
  • Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

Stigmalactam from Orophea Enterocarpa Induces Human Cancer Cell Apoptosis Via a Mitochondrial Pathway

  • Banjerdpongchai, Ratana;Wudtiwai, Benjawan;Pompimon, Wilart
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10397-10400
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    • 2015
  • Stigmalactam, an aristolactam-type alkaloid extracted from Orophea enterocarpa, exerts cytotoxicity against several human and murine cancer cell lines, but the molecular mechanisms remain elusive. The aims of this study were to identify the mode and mechanisms of human cancer cell death induced by stigmalactam employing human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells as models, compared to normal murine fibroblasts. It was found that stigmalactam was toxic to HepG2 and MDA-MB-231 cells with $IC_{50}$ levels of $23.0{\pm}2.67{\mu}M$ and $33.2{\pm}4.54{\mu}M$, respectively, using MTT assays. At the same time the $IC_{50}$ level towards murine normal fibroblast NIH3T3 cells was $24.4{\pm}6.75{\mu}M$. Reactive oxygen species (ROS) production was reduced in stigmalactam-treated cells dose dependently after 4 h of incubation, indicating antioxidant activity, measured by using 2',7',-dichlorohydrofluorescein diacetate and flow cytometry. Caspase-3 and caspase-9 activities were increased in a dose response manner, while stigmalactam decreased the mitochondrial transmembrane potential dose-dependently in HepG2 cells, using 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, indicating mitochondrial pathway-mediated apoptosis. In conclusion, stigmalactam from O. enterocarpa was toxic to both HepG2 and MDA-MB-231 cells and induced human cancer HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway.

Anti-adipogenic effect of the flavonoids through the activation of AMPK in palmitate (PA)-treated HepG2 cells

  • Rajan, Priyanka;Natraj, Premkumar;Ranaweera, Sachithra S.;Dayarathne, Lakshi A.;Lee, Young Jae;Han, Chang-Hoon
    • Journal of Veterinary Science
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    • v.23 no.1
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    • pp.4.1-4.15
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    • 2022
  • Background: Flavonoids are natural polyphenols found widely in citrus fruit and peel that possess anti-adipogenic effects. On the other hand, the detailed mechanisms for the antiadipogenic effects of flavonoids are unclear. Objectives: The present study observed the anti-adipogenic effects of five major citrus flavonoids, including hesperidin (HES), narirutin (NAR), nobiletin (NOB), sinensetin (SIN), and tangeretin (TAN), on AMP-activated protein kinase (AMPK) activation in palmitate (PA)-treated HepG2 cells. Methods: The intracellular lipid accumulation and triglyceride (TG) contents were quantified by Oil-red O staining and TG assay, respectively. The glucose uptake was assessed using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay. The levels of AMPK, acetyl-CoA carboxylase (ACC), and glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and levels of sterol regulatory element-binding protein 2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) expression were analyzed by Western blot analysis. The potential interaction between the flavonoids and the γ-subunit of AMPK was investigated by molecular docking analysis. Results: The flavonoid treatment reduced both intracellular lipid accumulation and TG content in PA-treated HepG2 cells significantly. In addition, the flavonoids showed increased 2-NBDG uptake in an insulin-independent manner in PA-treated HepG2 cells. The flavonoids increased the AMPK, ACC, and GSK3β phosphorylation levels and decreased the SREBP-2 and HMGCR expression levels in PA-treated HepG2 cells. Molecular docking analysis showed that the flavonoids bind to the CBS domains in the regulatory γ-subunit of AMPK with high binding affinities and could serve as potential AMPK activators. Conclusion: The overall results suggest that the anti-adipogenic effect of flavonoids on PA-treated HepG2 cells results from the activation of AMPK by flavonoids.

Antitumor Activity of Bupleuri Radix and Artemisiae capillaris Herba and Synergistic Effect with Anticancer Drugs (시호(柴胡), 인진(茵蔯)의 간암세포(肝癌細胞)에 대한 항암활성(抗癌活性) 및 항암제(抗癌劑)와의 상승작용(相乘作用))

  • Son, Gap-Ho;Kim, Seong-Hun
    • The Journal of Korean Medicine
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    • v.16 no.2 s.30
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    • pp.414-432
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    • 1995
  • In order to prove the antitumer effect of Bupleuri Radix(BR) and Artemisiae capillaris Herba(ACH) experimently, studies were done. The antitumer effect against hepatic cancer such as Hep G2, PLC & Hep 313, and also th synergastic action was evaulatcd in the combined treatment with anticancer drugs using chiefly for liver cancer, such as mitomycin(MMC), cisplatin(CPT) and 5-fluorouracil(5-FU). The results were obtained as follows: 1. IC50 against Hep G2, Hep 3B and PLC was 15.5ug/ml, 25.4ug/ml, 31.25ug/ml in Mitomycin (MMC), 92.5ug/ml, 50.2ug/ml, 62.5ug/ml in cisplatin(CPT) and 125ug/ml in 5-fluouracil(5- FU) respectively. 2. The antitumor effect was shown in the all concentrations of ACH, BR and below 55%-Cytotoxic effect against Hep G2 as compared with the date of control was shown in the concentration of $10^{-4}g/ml$ above of BR but not in ACH and also BR and ACHI revealed the synergistic effect with MMC. 3. The antitumor effect was shown in the concentration of $10^{-5}g/ml$ above of ACH, BR and below 55%-Cytotoxic effect against Hep 3B as compared with the data of control was shown in the concentration of $10^{-5}g/ml$ above of ACH but not in BH and also BR & ACH revealed the svnergistic effect with MMC. 4. The antitumor effect was shown in the all concentrations of ACH, BR and 55%-Cytotoxic effect against PLC as compared with the data of control was shown in the concentration of $10^{-5}g/ml$ above of ACH but not in BR and also ACH revealed the synergistic effect with MMC. From the above results it was concluded that Artemisiae capillaris had antitumor effect against PLC, Hep 3B, Bupleuri Radix against Hep G2 and also MMC showed the most synergistic effect in the anticancer drugs.

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Asiatic Acid Promotes p21WAF1/CIP1 Protein Stability through Attenuation of NDR1/2 Dependent Phosphorylation of p21WAF1/CIP1 in HepG2 Human Hepatoma Cells

  • Chen, Jin-Yuan;Xu, Qing-Wen;Xu, Hong;Huang, Zong-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.963-967
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    • 2014
  • Previous studies have suggested anti-tumor effects of asiatic acid in some human cancer cell lines. This agent is reported to increase the levels of $p21^{WAF1/CIP1}$ in human breast cancer cell lines. However, the molecular mechanisms have not been established. Here we report that asiatic acid up-regulates $p21^{WAF1/CIP1}$ protein expression but not the level of $p21^{WAF1/CIP1}$ mRNA in HepG2 human hepatoma cells. Furthermore, we found that the asiatic acid induced increase of $p21^{WAF1/CIP1}$ protein was associated with decreased phosphorylation (ser-146) of $p21^{WAF1/CIP1}$. Knockdown of NDR1/2 kinase, which directly phosphorylates $p21^{WAF1/CIP1}$ protein at ser-146 and enhances its proteasomal degradation, increased the levels of $p21^{WAF1/CIP1}$ protein and eliminated the regulation of $p21^{WAF1/CIP1}$ stability by asiatic acid. At the same time, the expression of NDR1/2 kinase decreased during treatment with asiatic acid in HepG2 cells. Moreover, asiatic acid inhibited the proliferation of HepG2 cells, this being attenuated by knockdown of $p21^{WAF1/CIP1}$. In conclusion, we propose that asiatic acid inhibits the expression NDR1/2 kinase and promotes the stability of $p21^{WAF1/CIP1}$ protein through attenuating NDR1/2 dependent phosphorylation of $p21^{WAF1/CIP1}$ in HepG2 cells.

Antiproliferative and Antioxidative Activities of Methanol Extracts of Echinacea angustifolia (Echinacea angustifolia 메탄올 추출물의 암세포 증식억제 및 항산화 효과)

  • Lee Joon-Kyoung;Koo Seung-Ja
    • Korean journal of food and cookery science
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    • v.21 no.3 s.87
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    • pp.311-318
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    • 2005
  • Echinacea, also blown as the purple coneflower, is a herbal medicine that has been used for centuries, customarily as a treatment for the common cold, coughs, bronchitis, upper respiratory infections, and some inflammatory conditions. We investigated the effects of methanol extracts of Echinacea angustifolia on the cytotoxicity against cancer cells $(HepG_2,\;3LL,\;HL60,\;L1210)$ and antioxidative activity. From the test results, each part of Echinaceashowed a cytotoxic effect against the cancer cell lines, and this cytotoxic effect increased with increasing sample concentration. At 1.0 mg/mL concentration the relative cytotoxic activities of the flower bud, leaf, stern and root parts were $90.5\%,\;52.7\%,\;37.1\%\;and\;19.2\%$, respectively, in $HepG_2$ cells, and $75.5\%,\;93.3\%,\;81.2\%,\;and\;75.1\%$ respectively, in HL60 cells, as evaluated by MTT assay. $IC_{50}(50\%\;inhibitory\;concentration)$ of the methanol extracts of the Echinacea flower bud was 0.214 mg/mL on /$HepG_2$ cells, and that of the Echinacea leaf and root was 0.166 mg/mL and 0.210 mg/mL, respectively, on HL60 cells. After /$HepG_2$ cells were incubated for 6 days at $37^{\circ}C$ with various concentrations of each part, the cell number increased while the inhibition rate on the /$HepG_2$ cell growth decreased. The antioxidative activities of the flower bud, leaf, stem and root parts were $59.0\%$ (0.75 mg/mL), $80.76\%$ (0.5 mg/mL), $95.5\%$ (0.25mg/mL) and $98.15\%$ (0.25 mg/mL), respectively, as evaluated by electron donating ability. These results indicated that Echinacea angustifolia has strong anticancer and antioxidative effects in vitro.

An Analytical Research of ONGABO with the Sovereign, Minister, Assistant and Courier Principle (君臣佐使論) on the Basis of HepG2 Cell Viability (간암세포주의 세포생존율에 근거한 온가보(溫家寶)(홍삼, 당귀, 오미자, 토사자, 울금)의 군신좌사론적(君臣佐使論的) 해석(解釋))

  • Hwang, Sung-Yeoun;Jeong, Kyung-Chae;Ahn, Seong-Hun
    • Journal of TMJ Balancing Medicine
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    • v.3 no.1
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    • pp.15-22
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    • 2013
  • Objectives and Methods: This study was conducted to investigate the formula of ONGABO to composed of Ginseng Radix (Red Ginseng), Angelica Gigantis Radix, Schisandrae Fructus, Cuscuta Semen, Curcumae Tuber with the method to observe the cell viability of HepG2 in the basic principle of oriental medicine formula study, Sovereign, Minister, Assistant and Courier principle (君臣佐使論). Results: Ginseng Radix (Red Ginseng) and Schisandrae Fructus were having a cell protection effect in HepG2 significantly. Angelica gigantis radix was decreased the cell viability of HepG2 significantly, and there were no effects for Cuscuta Semen and Curcumae Tuber to the cell viability of HepG2. Conclusions: As the above results, in the Sovereign, Minister, Assistant and Courier principle (君臣佐使論), Ginseng Radix (Red Ginseng) corresponds to sovereign medicinal having cell protect effects, angelica gigantis radix corresponds to minister medicinal having cell killing effects, Schisandrae Fructus corresponds to assistant medicinal to help red ginseng having cell protect effects. Cuscuta Semen and Curcumae Tuber correspond to courier medicinal having no effect in cell viability in HepG2. We hope the advanced research on sovereign, minister, assistant and courier principle will be proceed in the tomorrow.

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Nelumbo nucifera Leaves Extract Reduced the Production of Hepatitis B Surface Antigen on HepG2.2.15 (연잎추출물의 B형 간염 표면 항원 발현 억제 효과)

  • Lee, Yun-Hee;Kang, Li-Jung;Lee, Seong-Gene
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.2
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    • pp.133-138
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    • 2009
  • Nelumbo nucifera (lotus) is known to be a useful medicinal plant and leaf extract contains several flavonoids and alkaloids. To analyze the effect of Nelumbo nucifera leaves extract (NNL) on the HBsAg production, we treated NNL on HepG2.2.15 cells which contain the hepatitis B viral genome and secrete surface antigen into media. NNL suppressed the production of hepatitis B surface antigen as a dose-dependent manner. To analyze the effect of NNL on HBV DNA replication, PCR analysis was performed. NNL was not affected the HBV DNA replication and HBsAg mRNA expression. To understand the effect of NNL on the production of HBsAg, we carried out the analysis of lipid-metabolizing gene expression using one-step RT-PCR. NNL reduced the gene expression of FASN and SREBP2 and increased the expression of LDLR. Triglyceride content of HepG2.2.15 cells was not decreased by treatment of NNL. This result suggests a possibility that NNL may have an effect for the inhibition of hepatitis B surface antigen by modulation of lipid and cholesterol metabolism.

Hepatopotective Effects of Black Rice on Superoxide Anion Radicals in HepG2 Cells

  • Shim, Sang-In;Chung, Jin-Woong;Lee, Jeong-Min;Hwang, Kwon-Tack;Sone, Jin;Hong, Bum-Shik;Cho, Hong-Yon;Jun, Woo-Jin
    • Food Science and Biotechnology
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    • v.15 no.6
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    • pp.993-996
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    • 2006
  • Cyanidin 3-glucoside (C3G) isolated from black rice was investigated for hepatoprotective effects in HepG2 cells under oxidative stress. When an increase in the production of reactive oxygen species (ROS) was induced by gramoxone, cell viability was drastically decreased by 42%. However, in the presence of C3G, no hepatocytic damage was observed in HepG2 cells treated with gramoxone. C3G was found to manifest a stronger scavenging effect (91%) on superoxide anion radical ($O_2\;^{.-}$) than any of the other natural and synthetic antioxidants. Results suggest that C3G from black rice possesses hepatoprotective effects in vitro, which may be, at least in part, due to $O_2\;^{.-}$ scavenging.