• BMB Reports
• /
• 제43권9호
• /
• pp.599-603
• /
• 2010

Troglitazone is an anti-diabetic agent that improves hyperglycemia by reducing peripheral insulin resistance in type II diabetic patients. Troglitazone has been shown to cause growth inhibition of various normal and cancerous cells. However, the molecular mechanism by which troglitazone affects the growth of these cancer cells remains unclear. Here, we report that troglitazone treatment of Hep 3B human hepatocellular carcinoma cells resulted in dose-dependent growth inhibition. Analysis of cell cycle distribution by flow cytometry showed that the number of apoptotic cells was increased in a dose-dependent manner in response to troglitazone treatment. cDNA microarray analysis showed a number of differentially expressed genes in response to troglitazone. Among the upregulated genes, hypoxia-inducible factor 1 (HIF-1)-responsive RTP801 was induced in a dose-dependent manner. We also observed HIF-1 accumulation by immnocytochemistry after troglitazone treatment. These results strongly suggest that RTP801 might be involved in troglitazone-induced apoptosis in Hep 3B cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권4호
• /
• pp.1331-1336
• /
• 2015

Natural glycoproteins can induce apoptosis of tumor cells and exert anti-tumor activity by immunomodulatory functions, cytotoxic and anti-inflammation effects, and inhibition of endothelial growth factor. Given their prospects as novel agents, sources of natural antitumor glycoproteins have attracted attention and new research directions in glycoprotein biology are gradually shifting to the direction of cancer treatment and prevention of neoplastic disease. In this review, we summarize the latest findings with regard to the tumor suppressor signature of glycoproteins and underlying regulatory mechanisms.

• Journal of Microbiology and Biotechnology
• /
• 제12권4호
• /
• pp.702-705
• /
• 2002

Apicularen A (Api A) was recently isolated from Chondromyces sp. as a potent antitumor agent. Because of its unique chemical structure, a macrolide with a highly unsaturated amide side chain, and potent growth inhibitory effect in various cancer cell lines, Api A is currently in clinical trial for cancer therapy. In the present study, the effect of Api A on in vitro angiogenesis of bovine aortic endothelial cells (BAECS) was investigated. Api A potently inhibited the proliferation of BAECS in a dose-dependent manner. Treatment of the endothelial cells with up to 10 ng/ml of the compound did not show any cytotoxicity. In addition, it inhibited basic fibroblast growth factor (bFGF)-induced invasion and capillary tube formation of BAECS at concentrations of 2-5 ng/ml. These results, therefore, demonstrate that Apl A is a novel antiangiogenic agent and may suppress the growth of tumors, at least in part, by the inhibition of neovascularization.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권16호
• /
• pp.6581-6586
• /
• 2014

Background: The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kr$\ddot{u}$ppel-like factor 4 (klf4) is a zinc finger-containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors. Aims: In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells. Materials and Methods: The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR andto ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit. Results: Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment. Conclusions: Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.

• BMB Reports
• /
• 제33권3호
• /
• pp.213-220
• /
• 2000

A fulminant hepatitis is associated with massive liver cell necrosis and a high mortality rate. But survivors regenerate a normal liver and do not have chronic liver disease. This clinical course suggests that the acutely injured livers release a factor that allows a recovery from chronic hepatitis or cirrhosis. The objective of this study was to isolate and characterize an anti-fibrotic factor from acutely damaged rat livers. The liver cell necrosis was prepared from rat by warm ischemical perfusion and the perfusates were assessed against the growth inhibition of fat-storing cells (FSC). A liver-derived growth inhibitory factor (LDGIF) was purified from ischemically damaged rat livers by chromatographies on Sephacryl S-300, CM Sepharose, hydroxyapatite, and Superose 12. The LDGIF was isolated with an overall purification of 194-fold and 40% recovery. Although LDGIF was identified as the rat liver arginase by Nterminal sequence analysis, LDGIF exists as a monomer and the purified native arginase has a trimer form. Furthermore, LDGIF has a lower enzyme activity on the hydrolysis of L-arginine and a higher inhibitory effect on proliferation of FSC than the normal rat liver arginase. The catalytic activity of LDGIF is ascribed to the monomeric characteristics of the LDGIF. Therefore, the inhibitory action of LDGIF might not be due to the arginine depletion by the catalytic activity of arginase. In conclusion, the presence of the LDGIF could interpret the clinical course that serious fibrosis is not found in the liver of patients recovering from severe hepatic necrosis due to fulminant hepatitis, suggesting that this LDGIF may provide a novel target for the prevention and treatment of hepatic fibrosis.

• International Journal of Oral Biology
• /
• 제43권2호
• /
• pp.61-68
• /
• 2018

Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

• Journal of Ginseng Research
• /
• 제20권1호
• /
• pp.15-22
• /
• 1996

In order to investigate the Immunomodulatory effects of ginseng, we have studied the effects of ginseng saponin on the proliferation and cytosine gene expression of human pheripheral blood mononuclear cell (PBMC). In the PBMC proliferation assay, total saponin exhibited proliferation inhibition on the PBMC or phytohemagglutinin(PHA)-stimulated PBMC in a dose-dependent fashion. Immunomodulatory effects of ginseng were further investigated using the cytokine gene expression as the indicators. In the reverse transcription-polymerase chain reaction (RT-PCR) test, interleukin (IL)-1, IL-2, IL-3, IL-4, IL-6, IL-13, granulocyte macrophage-colony stimulating factor, tumor necrosis factor (TNF), migration inhibitory factor and transforming growth factor genes were expressed in the PHA-stimulated PBMC 48 hrs after cell culture. Among expressed cytokines, total saponin could increase the expression of IL-1 and TNF of PBMC without stimulation of PHA. All of ginsenosides, $Rb_1$, $Rb_2$, $Rg_1$, Rc, Re, incresed TNF gene expression. Especially, Rb2 (20 g/ml) showed most prominent effect on TNF gene expression and it also slightly increased IL-1 gene expression of PBMC.

• BMB Reports
• /
• 제50권12호
• /
• pp.599-600
• /
• 2017

Many studies have focused on the tumor suppressive role of $TGF-{\beta}$ signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of $TGF-{\beta}$ inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, $TGF-{\beta}$ inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical $TGF-{\beta}$ signaling in tumorigenesis. Moreover, we found that Snail is the target gene of the $TGF-{\beta}$ signaling pathway that promotes hepatic carcinogenesis. The knockdown of Snail suppressed the early tumorigenesis in the liver, as did the $TGF-{\beta}$ inhibition, while the ectopic expression of Snail restored tumorigenesis that was suppressed by the $TGF-{\beta}$ inhibition. Our findings establish the oncogenic $TGF-{\beta}$-Smad-Snail signaling axis during the early tumorigenesis in the liver.

• BMB Reports
• /
• 제28권5호
• /
• pp.464-470
• /
• 1995

Quinolone antibiotics are DNA gyrase inhibitors, but their bactericidal action seems to involve more than the inhibition of DNA gyrase activity. Hence, the potentially crucial factors among possible mechanisms of quinolone action; cleavable complex formation, inhibition of DNA synthesis, and induction of SOS response were investigated. These parameters were measured in an Escherichia coli strain exposed to quinolones in the logarithmic growth phase, and correlated with the bactericidal activity of quinolones. Cleavable complex formation proved to be the factor most related to bactericidal action. Inhibition of DNA synthesis was substantially correlated with bactericidal activity, but induction of SOS response was least correlated with bactericidal activity. Therefore, it was concluded that quinolones exert bactericidal action primarily through cleavable complex formation, and subsequent unknown cellular processes together with inhibition of DNA synthesis contribute to the bactericidal activity of quinolones.

• 한국식품영양학회지
• /
• 제22권4호
• /
• pp.542-547
• /
• 2009

Brine mineral water(BMW) has recently gained attention as a new water resource due to its biological activities. In this study, BMW from the Geumjin area(Gangneung-city, Korea) was evaluated for its growth inhibition, anti-metastasis and anti-angiogenesis activity against cancer cells. The in vitro cytotoxicity was measured by CCK assay, and the anti-metastasis activity was estimated by lung metastasis in vivo. The in vitro incubation of mouse splenic cells with BMW that had been diluted more than 4-fold showed no effect on the cell growth when compared to a control group. Additionally, BMW inhibited the growth of the EL-4, L5178Y-R and colon26-M3.1 cancer cell lines in a dose-dependent manner. In vivo evaluation of the anti-metastasis activity of BMW in BALB/c mice inoculated with the colon26-M3.1 cell line revealed dose-dependent inhibition in response to treatment with samples that were diluted by up to 9 times. Finally, treatment with BMW effectively suppressed the growth of vascular endothelial growth factor(VEGF) added human umbilical vein endothelial cells. Overall, these results suggest that BMW has anti-cancer activity.