• Biomolecules & Therapeutics
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• 제18권4호
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• pp.402-410
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• 2010

Although the overproduction of prostaglandin $E_2$ ($PGE_2$) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying $PGE_2$-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating $PGE_2$-mediated signaling pathway. $PGE_2$ stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. $PGE_2$ also increased the phosphorylation of GSK-$3{\beta}$, the translocation of ${\beta}$-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited $PGE_2$-induced growth stimulation and also suppressed $PGE_2$-mediated signal transduction, as well as ${\beta}$-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7825-7829
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• 2014

Objective: To investigate the effect of high expression of XAF1 in vivo or in vitro on lung cancer cell growth and apoptosis. Methods: 1. The A549 human lung cancer cell line was transfected with Ad5/F35 - XAF1, or Ad5/F35 - Null at the same multiplicity of infection (MOI); (hereinafter referred to as transient transfected cell strain); XAF1 gene mRNA and protein expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting respectively. 2. Methyl thiazolyl tetrazolium (MTT) and annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis before and after infection of Ad5/F35 - XAF1 with Western blotting for apoptosis related proteins, caspase 3, caspase - 8 and PARP. 3. After the XAF1 gene was transfected into lung cancer A549 cells by lentiviral vectors, and selected by screening with Blasticidin, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were applied to detect mRNA and protein expression, to establish a line with a stable high expression of XAF1 (hereinafter referred to as stable expression cell strain). Twenty nude mice were randomly divided into groups A and B, 10 in each group: A549/XAF1 stable expression cell strain was subcutaneously injected in group A, and A549/Ctrl stable cell line stable expression cell strain in group B (control group), to observe transplanted tumor growth in nude mice. Results: The mRNA and protein expression of XAF1 in A549 cells transfected by Ad5/F35 - XAF1 was significantly higher than in the control group. XAF1 mediated by adenovirus vector demonstrated a dose dependent inhibition of lung cancer cell proliferation and induction of apoptosis. This was accompanied by cleavage of caspase -3, -8, -9 and PARP, suggesting activation of intrinsic or extrinsic apoptotic pathways. A cell strain of lung cancer highly expressing XAF1 was established, and this demonstrated delayed tumor growth after transplantation in vivo. Conclusion: Adenovirus mediated XAF1 gene expression could inhibit proliferation and induce apoptosis in lung cancer cells in vitro; highly stable expression of XAF1 could also significantly inhibit the growth of transplanted tumors in nude mouse, with no obvious adverse reactions observed. Therefore, the XAF1 gene could become a new target for lung cancer treatment.

• 대한의생명과학회지
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• 제15권2호
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• pp.105-112
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• 2009

The screening of the anti-cancer activity of the chemical library provided 2-thio-4-aminopyrimidine as the initial hit. The confirmation of structure and biological effect of hit was performed by synthesis and biological evaluation. The optimization of hit was performed by derivatization of substituents while keeping the core structure. The evaluation of growth inhibitory activity was carried out using SRB assay against 6 human cancer cell lines and human fibroblast. The growth inhibitory activity of compounds showed substituent dependency and more than 5 compounds showed complete growth inhibition of cancer cell lines at 10 ${\mu}M$ concentration. Chemical library screening followed by synthetic modification provided possibility that 2-thio-4-aminopyrimidine can be used as a new scaffold for the development of anti-cancer agent.

• Tuberculosis and Respiratory Diseases
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• 제75권1호
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• 한국식품영양학회지
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• 제5권1호
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• pp.13-22
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• 1992

This study was divised to observe the inhibitory effect of growth rate of human colon cancer cells by Eucommial leaf extract, in vitro. Three species of human colon cancer cells, HRT-18, HCT-48 and HT-29, were used for the experiment. Each extract of Eucommial leaf was prepared by extraction with water, 95% alcohol, acetone, chloroform and petroleum ether, and then the inhibitory effect of each extract on the growth rate of cells was compared with control group and each other. The experimental results obtained are summarized as follows; 1. Inhibitory effects on growth rate of human colon cancer fells were strongest in the petroleum ether extract and next in the chloroform extract. 2. Inhibitory effects on the growth rate of the cancer cells by extracts of water, 95% alcohol and acetone were weaker than that of petroleum ether and chloroform. 3. Inhibitory effect of each extract on the cancer cell growth was shown most strong activity in HT-29, and was in order of HRT 18 and HCT-48. In view of the results, it could be suggested that inhibitory effects of non-polar solvent's extracts against the cancer cell growth were more stronger than that of polar solvents and the effects were indicated difference according to the species of the cells.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권3호
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• pp.207-210
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• 2000

When endothelial cells isolated isolated from human umbilical venis were cultred for 6dary using 96-well microplates, the final cell density in each was fiund not to be the same although the medium composition of each well was exactly the same. Cell growth in the wells located at the periphery of a microplate was low, while that in the central area of the plate was high. A possible cause for different rate of growth was proposed as the uneven concentration of oxygen in the culture medium of each well.

• Natural Product Sciences
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• 제10권2호
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• pp.74-79
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• 2004

Dietary flavonoids are currently receiving considerable attention in developing novel cancer-preventive approaches because of their potential capacities to actively induce apoptosis of cancer cells. In our previous report, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein and named RCMF (RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) that is traditionally used as food additive and herbal medicine. In this study, we evaluated the effects of the RCMF on cell proliferation and apoptosis using SV40-transformed tumorigenic hepatocytes, BNL SV A.8. Tritium uptake assay showing the proliferative capacity of the cells was strongly suppressed in the presence of RCMF. This anti-proliferative effect was further confirmed through trypan blue exclusion. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increase in DNA fragmentation, low fluorescence intensity in nuclei after propidium iodide staining, and the appearance of DNA laddering. Collectively, this study demonstrated that RCMF can be approached as a potential agent that is capable of significantly inhibiting cell growth of hepatic cancer cells.

• 한국환경성돌연변이발암원학회지
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• 제24권2호
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• pp.51-66
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• 2004

Retinoids, better known as vitamin A, have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoids can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. We have examine the effect of all-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) on human breast cancer cell(MCF-10A, T47-D, MCF-7) proliferation using MTT assay and cell cycle analysis(FACS). Overexpression of cyclin D1 protein is observed in the majority of breast cancers, suggesting that dysregulated expression of cyclin D1 might be a critical event in breast cancer carcinogenesis. We investigated whether tRA and 9-cis RA might affect expression of cyclin D1 on human breast cancer cells(MCF-10A, T47-D, MCF-7) using RT-PCR and west-ern bolt. In MCF-10A cells, either tRA or 9-cis RA treatment did not affect the cell proliferation. In T47-D cells and MCF-7 cells, either tRA or 9-cis RA treatment showed the inhibition of the cell proliferation over control cells and also inhibit the estrogen stimulated cell proliferation when it was given together with estrogen. The effect of retinoids was dose- and time- dependent. T47-D cells treated with 1.0 $\muM$ tRA undergo G0/G1-phase arrest by Day 5. MCF-7 cells treated with 1.0 $\muM$ tRA undergo S-phase arrest by Day 5. All-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) inhibited the cyelin D1 mRNA and protein expression levels of human MCF-7 and T47-D breast carcinoma cells in vitro. The data indicate that retinoids can reduce cyclin D1 expression levels in a variety of breast cell lines in vitro and result in inhibition of cell proliferation. tRA-mediated growth inhibition and cyclin D1 expression inhibition is more potent than 9-cis RA mediated that. tRA-mediated inhibition effect is more potent on T47-D cells than on MCF-7 cells. Our data suggest that retinoids activity is different according to property of cell lines. Future chemoprevention of breast cancer studies using retinoids will be necessary to determine the mechanism of the retinoids-mediated growth inhibition.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1677-1682
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• 2015

Cancer progression is attained by uncontrolled cell division and metastasis. Increase in tumor size triggers different vascular channel formation to address cell nutritional demands. These channels are responsible for transferring of nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by numerous factors including vascular endothelial growth factors (VEGFs). These factors play an important role during embryonic development. Members included in this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence cellular growth and apoptosis. Being freely diffusible these proteins act in both autocrine and paracrine fashions. In this review, genetic characterization these molecules and their putative role in cancer staging has been elaborated. Prognostic significance of these molecules along with different stages of cancer has also been summarized. Brief outline of ongoing efforts to target hot spot target sites against these VEGFs and their cognate limitations for therapeutic implications are also highlighted.

• Journal of Nutrition and Health
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• 제49권2호
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• pp.72-79
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• 2016

Purpose: The initiation of mandatory folic acid fortification using pteroylmonoglutamic acid (PteGlu) has reduced the rate of congenital malformations. However, it also appears to be responsible for several adverse effects, including increased cancer incidence. This may be related to physicho-chemical characteristics of PteGlu. This study examines the potential effect of high concentrations of PteGlu on a population subjected to mandatory folic acid fortification using an in vitro model. Methods: Caco-2 (colorectal cancer) and MCF7 (breast cancer) cell lines were cultured at 6 different PteGlu concentrations (0, 0.1, 1, 50, 250, and $500{\mu}g/ml$) for 6 days. Cell growth was determined using thiazolyl blue tetrazolium bromide assay. The genotype of dihydrofolate reductase 19bp deletion/insertion (DHFR 19-del) was also scored in cell lines using a restriction fragment length polymorphism technique to examine whether genetic variations may factor in cell proliferation. Results: PteGlu exhibited differential growth promoting properties between cell lines. Caco-2 cells did not show a significant growth difference at low concentrations compared to control, however, at higher concentrations, the growth showed a contrasting trend in the early experimental period, while MCF7 showed enhanced cell growth at all concentrations. The DHFR 19-del genotype differed in the two cell lines. Conclusions: Altered response to PteGlu by Caco-2 and MCF7 may reflect a tissue specific disease aetiology or genotype specific differential enzyme activity, for example by DHFR, to critical levels of PteGlu. As folic acid fortification is a blanket intervention, and DHFR and other enzyme activities vary between individuals, PteGlu intake may have an as yet undefined effect on health. These findings may be relevant when considering mandatory folic acid fortification for disease prevention.