• Title, Summary, Keyword: cell proliferation/drug effects

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Differential Effects of Nongenotoxic and Genotoxic Carcinogen on Cell Proliferation and c-Jun Expression in the Rat Liver Initiated with Diethylnitrosamine

  • Kim, Hye-Jin;Kim, Jong-Won;Hong, Jin-Tae;Nam, Ki-Taek;Kim, Dae-Joong
    • Environmental Mutagens and Carcinogens
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    • v.19 no.2
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    • pp.89-94
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    • 1999
  • Cell proliferation and c-Jun expression pattern in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate, and genotoxic carcinogen 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) were investigated to see whether differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation. Male F344 rats were initially given a single intraperitioneal injection of diethylnitrosamine (200 mg/kg body weight), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CE or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to the two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed until 8 weeks. Cell proliferation was examined by immunohistochemical staining of bromodeoxyuridine and c-Jun expression was determined by northern blotting. The increase of cell proliferation rate after PH was significant in the rats fed 0.05% IQ and continued until 8 weeks, while the increase was not significant in the rats fed phenobarbital and clofibrate compared to that in the rats fed control diet. mRNA level of c-Jun in the liver treated with IQ was about 7 fold higher than that of control and peak at 5 hours after rH. In the liver treated with CE, mRNA level of c-Jun was 3-4 fold higher than that of control and the highest level of mRNA of c-Jun was seen at 24 hours after PH. These results show that differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation pattern.

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Effects of Free Anthraquinones Extract from the Rhubarb on Cell Proliferation and Accumulation of Extracellular Matrix in High Glucose Cultured-Mesangial Cells

  • Wang, Jianyun;Fang, Hui;Dong, Bingzheng;Wang, Dongdong;Li, Yan;Chen, Xiao;Chen, Lijuan;Wei, Tong;Wei, Qunli
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.6
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    • pp.485-489
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    • 2015
  • Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidney, but the efficacy of currently available strategies for the prevention of DN remains unsatisfactory. In this study, we investigated the effects of free anthraquinones (FARs) extract, which was extracted from the rhubarb and purified by macroporous resin DM130 with gradient mixtures of ethanol/water as the lelution solvents, in high glucose-cultured glomerular mesangial cells (MCs). The cell proliferation was determined by CCK-8 assay, the levels of TGF-${\beta}1$, CTGF, ColIV and FN proteins in the supernatant of MCs were measured by ELISA assays, and the mRNA levels of these four genes were detected by RT-PCR. The results showed that the increased proliferation of MCs, the mRNA levels and protein expression of TGF-${\beta}1$, CTGF, ColIV and FN induced by high glucose were inhibited after the treatment with the FARs extract. This indicated that FARs extract could inhibit cell proliferation and the expression of main extracellular matrix induced by high glucose in MCs. The FARs extract exhibited potential values for prophylaxis and therapy of DN.

Emodin Inhibits Breast Cancer Cell Proliferation through the ERα-MAPK/Akt-Cyclin D1/Bcl-2 Signaling Pathway

  • Sui, Jia-Qi;Xie, Kun-Peng;Zou, Wei;Xie, Ming-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6247-6251
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    • 2014
  • Background: The aim of the present study was to investigate the involvement of emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the estrogen (E2) signal pathway in vitro. Materials and Methods: MTT assays were used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA-MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the effects of emodin on the expression of estrogen receptor ${\alpha}$, cyclin D1 and B-cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess transcriptional activity of $ER{\alpha}$. Results: Emodin could inhibit E2-induced MCF-7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in G0/G1 phase, further blocking the effect of E2 on expression and transcriptional activity of $ER{\alpha}$. Moreover, Emodin influenced the ER ${\alpha}$ genomic pathway via downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non-genomic pathway via decreased PI3K/Akt protein expression. Conclusions: These findings indicate that emodin exerts inhibitory effects on MCF-7 cell proliferation via inhibiting both non-genomic and genomic pathways.

Inhibitory Effects of α-Pinene on Hepatoma Carcinoma Cell Proliferation

  • Chen, Wei-Qiang;Xu, Bin;Mao, Jian-Wen;Wei, Feng-Xiang;Li, Ming;Liu, Tao;Jin, Xiao-Bao;Zhang, Li-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3293-3297
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    • 2014
  • Background: Pine needle oil from crude extract of pine needles has anti-tumor effects, but the effective component is not known. Methods: In the present study, compounds from a steam distillation extract of pine needles were isolated and characterized. Alpha-pinene was identified as an active anti-proliferative compound on hepatoma carcinoma BEL-7402 cells using the MTT assay. Results: Further experiments showed that ${\alpha}$-pinene inhibited BEL-7402 cells by arresting cell growth in the G2/M phase of the cell cycle, downregulating Cdc25C mRNA and protein expression, and reducing cycle dependence on kinase 1(CDK1) activity. Conclusion: Taken together, these findings indicate that ${\alpha}$-pinene may be useful as a potential anti-tumor drug.

Luteolin Inhibits Proliferation Induced by IGF-1 Pathway Dependent ERα in Human Breast Cancer MCF-7 Cells

  • Wang, Li-Meng;Xie, Kun-Peng;Huo, Hong-Nan;Shang, Fei;Zou, Wei;Xie, Ming-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1431-1437
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    • 2012
  • The growth of many breast tumors is stimulated by IGF-1, which activates signal transduction pathways inducing cell proliferation. $ER{\alpha}$ is important in this process. The aim of the study was to investigate relationships in vitro among inhibitory effects of luteolin on the growth of MCF-7 cells, IGF-1 pathway and $ER{\alpha}$. Our results showed that luteolin could effectively block IGF-l-stimulated MCF-7 cell proliferation in a dose- and time-dependent manner and block cell cycle progression and induce apoptosis evidenced by the flow cytometric detection of sub-G1DNA content. Luteolin markedly decreased IGF-l-dependent IGF-IR and Akt phosphorylation without affecting Erk1/2 phosphorylation. Further experiments pointed out that $ER{\alpha}$ was directly involved in IGF-l induced cell growth inhibitory effects of luteolin, which significantly decreased $ER{\alpha}$ expression. Knockdown of $ER{\alpha}$ in MCF-7 cells by an $ER{\alpha}$-specific siRNA decreased the IGF-l induced cell growth inhibitory effects of luteolin. $ER{\alpha}$ is thus a possible target of luteolin. These findings indicate that the inhibitory effect of luteolin on the growth of MCF-7 cells is via inhibiting IGF-l mediated PI3K-Akt pathway dependent of $ER{\alpha}$ expression.

The Cytotoxic and Anti-proliferative Effects of 3-Hydrogenkwadaphnin in K562 and Jurkat Cells Is Reduced by Guanosine

  • Moosavi, Mohammad Amin;Yazdanparast, Razieh;Sanati, Mohammad Hasan
    • BMB Reports
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    • v.38 no.4
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    • pp.391-398
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    • 2005
  • 3-hydrogenwadaphnin (3-HK) is a new daphnane-type diterpene ester isolated from Dendrostellera lessertii with strong anti-tumoral activity in animal models and in cultures. Here, prolonged effects of this new agent on proliferation and viability of several different cancerous cell lines were evaluated. Using [$^3H$]thymidine incorporation, it was found that the drug inhibited cell proliferation and induced G1/S cell cycle arrest in leukemic cells 24 h after a single dose treatment. The cell viability of Jurkat cells was also decreased by almost 10%, 31% and 40% after a single dose treatment (7.5 nM) at 24, 48 and 72 h, respectively. The drug-treated cells were stained with acridine orange/ethidium bromide to document the chromatin condensation and DNA fragmentation. These observations were further confirmed by detection of DNA laddering pattern in the agarose gel electrophoresis of the extracted DNA from the treated cells. Treatment of K562 cells with the drug at 7.5, 15 and 30 nM caused apoptosis in 25%, 45% and 65% of the cells, respectively. Exogenous addition of $25-50\;{\mu}M$ guanosine and/or deoxyguanosine to the cell culture of the drug-treated cells restored DNA synthesis, released cell arrest at G1/S checkpoint and decreased the apoptotic cell death caused by the drug. These observations were not made using adenosine. However, the drug effects on K562 cells were potentiated by hypoxanthine. Based on these observations, perturbation of GTP metabolism is considered as one of the main reasons for apoptotic cell death by 3-HK.

Experimental Effects of Sunjeonhwadok-Tang on the Proliferation of Cancer Cells and Immunocytes - Focusing around Combined Effects of Anticarcinogen - (선전화독탕(仙傳化毒湯)이 암세포(癌細胞) 및 면역세포(免疫細胞) 증식(增殖)에 미치는 실험적(實驗的) 효과(效果) - 항암제 병용효과를 중심으로 -)

  • Chang, Wen-Lih;Kim, Jong-Han;Park, Su-Yeon;Choi, Jung-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.18 no.1
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    • pp.104-115
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    • 2005
  • Sunjeonhwadok-Tang was a drug that treated carbuncle and cellulitis. So, the purpose of this study was to investigate effects of Sunjeonhwadok-Tang on the proliferation of cancer calls and immunocytes focusing around combined effects of anticarcinogen. We used Sunjeonhwadok-Tang extract(SHT) with freeze-dried, 8wks-old male balb/c mice and cancer cell lines(L1210, Sarcoma-180) for this Study. The proliferation of cells was tested using a colorimetric tetrazoliun assay(MTT assay). The results : 1. SHT was significantly showed cytotoxicity on the L1210 cell lines. 2. SHT was significantly increased proliferation of thymocytes and splenocytes in vitro. 3. In combined effects of SHT and vincristine(0.005 mg/kg), SHT was significantly inhibited proliferation of L1210 cell lines, but was not inhibited proliferation of Sarcoma-180 cell lines compared with positive control group. 4. In combined effects of SHT and vincristine(0.005 mg/kg), SHT was significantly increased proliferation of thymocytes and splenocytes compared with positive control group. 5. In combined effects of SHT and vincristine, SHT was significantly increased proliferation of thymocytes and splenocytes in normal mice. 6. In combined effects of SHT and vincristine, SHT was significantly inhibited proliferation of L1210 cells in L1210 cells transplanted mice 7. In combined effects of SHT and vincristine, SHT was significantly increased proliferation of L1210 cell in L1210 cells transplanted mice. The present author thought that SHT had action of anti-cancer and immuno-activity, and in combined effects of vincristine, SHT had recoverable effects on damage by anticarcinogen.

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The Combined Effect of Moschus and Anti-tumor drug Mitomycin C (사향과 항암제 Mitomycin C의 병용효과)

  • Eun Jae Soon;Kim Dae Keun;Song Jung Mo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.6
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    • pp.1404-1408
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    • 2003
  • The combined effects of water-soluble fraction of Moschus (ME) and anti-tumor drug mitomycin C on the proliferation of human tumor cell-lines were estimated by MTT colorimetric assay. ME inhibited the proliferation of Hep G2, A540, HeLa, KHOS-NP and Balb/c 3T3 cells. Also, ME increased the cytotoxicity of mitomycin C on Hep G2, A549 and HeLa cells. In addition, ME enhanced the cell viability of murine splenocytes and human lymphocytes at the concentration of 100㎍/㎖. These results indicate that ME inhibits the proliferation of human tumor cells and increases the cytotoxicity of mitomycin C without cytoxicity on immune cells.

Experimental Effects of Taklihwangki-Tang on the Anti-Cancer And Immuno-Action (托裏黃기湯이 抗癌 및 免疫作用에 미치는 實驗的 效果)

  • Jeong, Dong-Hwan;Choi, Jung-Hwa;Kim, Jong-Han;Jeong, Woo-Hyun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.15 no.2
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    • pp.118-130
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    • 2002
  • Taklihwangki-Tang was a drug that treated carbuncle and cellulitis. So, the purpose of this Study was to investigate effect of Taklihwangki-Tang on the anti-cancer and proliferation of immunocytes, nitric oxide(NO) production of peritoneal macrophages. We used Taklihwangki-Tang extract(THT) with freeze-dried, 8wks-old male mice and cancer cell lines(L1210, S-180) for this Study. The proliferation of cells was tested using a colorimetric tetrazoliun assay(MTT assay). The results of this Study were obtained as follow ; THT was showed cytotoxicity on the L1210 and S-180 cell lines, increased proliferation of thymocytes. And the combined effects of THT and vincristine were became cytotoxicity of cancer cell lines and increased significantly proliferation of thymocytes. THT accelerated proliferation of thymocytes in normal mice, and decreased significantly proliferation of L1210 cells and accelerated significantly NO production of peritoneal macrophages in L1210 cells transplanted mice. This results suggest that THT inhibit proliferation of cancer cells by becoming immunocytes activity(NO production, proliferation of T-cell).

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Experimental Study of Naesosan(內消散) on the Effects of Anti-Cancer (內消散의 抗癌效果에 관한 實驗的 硏究)

  • Park, Su-Yeon;Choe, Jeong-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.14 no.1
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    • pp.154-166
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    • 2001
  • Naesosan(NSS) has been used in Oriental Medicine as a drug that treated carbuncle and cellulitis. So, the purpose of this Study was to investigate effects of NSS on the cytotoxicity of cancer cell lines and lymphocytes in vitro, proliferation of Ll210 cells and lymphocytes in L1210 cells transplanted mice, improvement of blood count in Ll210 cells transplanted mice, tumor weight and body weight in sarcoma-180 cells transplanted mice, survival prolongation in sarcoma-180 cells transplanted mice. We used NSS extract with freeze-dried, 8wks-old male mice(balb/c and ICR mouse $18{\pm}2g$). Ll210 cell lines, and sarcoma-180 cell lines for this Study, The proliferation of cells was tested using a colorimetric tetrazoliun assay(MTT assay). The results of this Study were obtained as follows ; 1. NSS showed significantly cytotoxicitic effects of cancer cell lines, did not show cytotoxicitic effects of lymphocytes. 2, Proliferation of lymphocytes in L1210 cells transplanted mice did not effects by NSS. 3. NSS inhibited significantly the proliferation of L1210 cells in L1210 cells transplanted mice. 4. NSS improved significantly the blood count in Ll210 cells transplanted mice. 5. NSS increased significantly th body weight in sarcoma-180 cells transplanted mice. 6. NSS dereased significantly the tumor weight in sarcoma-180 cells transplanted mice. 7. NSS prolonged significantly the survival time in sarcoma-180 cells transplanted mice.

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