• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3711-3719
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• 2016

Drawbacks of conventional cancer treatments, with lack of specificity and cytotoxicity using current approaches, underlies the necessity for development of a novel approach, gene-directed cancer therapy. This has provided novel technological opportunities in vitro and in vivo. This review focuses on a member of an apoptosis inhibitor family, survivin, as a valuable target. Not only the gene but also its promoter are applicable in this context. This article is based on a literature survey, with especial attention to RNA interference as well as tumor-specific promoter action. The search engine and databases utilized were Science direct, PubMed, MEDLINE and Google. In addition to cell-cycle modulation, apoptosis inhibition, interaction in cell-signaling pathways, cancer-selective expression, survivin also may be considered as specific target through its promoter as a novel treatment for cancer. Our purpose in writing this article was to create awareness in researchers, emphasizing relation of survivin gene expression to potential cancer treatment. The principal result and major conclusion of this manuscript are that survivin structure, biological functions and applications of RNA interference systems as well as tumor-specific promoter activity are of major interest for cancer gene therapy.

• The Journal of Pediatrics of Korean Medicine
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• v.27 no.1
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• pp.59-68
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• 2013

Objectives The aim of this study is to investigate whether hwang-ryun-haedok-tang (HDT) affect proliferations of androgen-dependent LNCaP prostate cancer cells, androgen-independent PC-3, DU-145 prostate cancer cells, MCF-7 human breast cancer cells, A549, NCI-H292 human pulmonary cancer cells and K-562 human chronic myelogenous leukemia cells. Materials and Methods Effects of HDT on proliferations of each cancer cell line were investigated. 20,000 cells/well were plated in each well of 96-well culture plate. After 24 hrs, 0.01-10% of HDT in culture medium was added to cancer cells. The number of cells was counted by using SRB assay or direct cell counting method after 72 hours from drug treatment. Effect of baicalein or berebrine on proliferation was assessed according to the same method. Results (1) HDT inhibited proliferations of LNCaP, PC-3 and DU-145 prostate cancer cells. (2) HDT inhibited proliferation of MCF-7 breast cancer cells. (3) HDT also inhibited proliferations of A549, NCI-H292 pulmonary cancer cells and K-562 chronic myelogenous leukemia cells. (4) Baicalein and berberine also showed inhibitory effects on proliferations of prostate and breast cancer cells. Conclusion : HDT inhibited proliferations of human prostate, breast, pulmonary and blood cancer cells. These results suggest us the potential use of HDT as a chemopreventive or chemotherapeutic agent. Effect of HDT on human cancer should be further investigated using in vivo experimental models that can reflect pathophysiology of human cancer through another studies.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.860-865
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• 2009

Osteoclasts are bone-resorbing multinucleated cells derived from the monocyte/macrophage lineage. The differentiation of osteoclasts are regulated by osteoblastic cells expressed RANKL, which is the most critical molecule for osteoclast differentiation. In this study, we found that water extracts of cuscuta inhibited RANKL-mediated osteoclast differentiation by direct action on bone marrow macrophages (BMMs) without cytotoxicity. In BMMs, water extracts of cuscuta inhibited the mRNA expression of c-Fos, NFATc1, TRAP, and OSCAR. Also, the protein expression of c-Fos and NFATc1 was inhibited by water extracts of cuscuta treatement. Water extracts of cuscuta inhibited the phosphorylation of p38, ERK, and JNK in BMMs treated with RANKL. However, water extracts of cuscuta did not inhibit RANKL-induced I-${\kappa}B$ activation. Water extract of cuscuta failed to inhibit bone resorption by osteoclasts cultured on hydroxyapatite plates. These results suggest that cuscuta may be a promising drug for use against bone disorders such as osteoporosis and rheumatoid arthritis.

• Toxicological Research
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• v.20 no.3
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• pp.241-250
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• 2004

We previously found that bisphenol A (BPA) caused neurotoxic behavioral alteration. Since disturbance of calcium homeostasis is an implicated contributor in the neurotoxic mechanism of environmental toxicants, we investigated whether BPA alters calcium homeostasis. Unlike other neurotoxic agents which cause increase of intracellular calcium level, BPA decreased $[Ca^{2+}]_i$ dose-dependently in PC12 cells and cortical neuronal cells regardless of the calcium existence in buffer. BPA at greater concentrations than 100 $\mu\textrm{M}$ reduced cell viability significantly in both types of cells. BPA also suppressed L-glutamate (L-type channel activator, 30 mM) and trifluoperazine (calmodulin antagonist, 30 $\mu\textrm{M}$)-induced increase of $[Ca^{2+}]_i$. BPA further lowered caffeine (RYR activator, 100 $\mu\textrm{M}$)-decreased $[Ca^{2+}]_i$, but did not alter dantrolene (RYR inhibitor, 100 $\mu\textrm{M}$), heparin (IP3 inhibitor, 200 units/ml) and xestospongin C (IP3 inhibitor, 5 $\mu\textrm{M}$)-decreased $[Ca^{2+}]_i$. Cell viability was not directly related to intracellular calcium change by bisphenol A that alternation of intracellular calcium may not be a direct causal factor of BPA-induced neuronal cell death.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.99-105
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• 2005

Perchloroethylene (tetrachloroethylene, PCE), a dry cleaning and degreasing solvent, can enter ground-water through accidental leak or spills. PCE can be degraded to trichloroethylene (TCE), 1, 1-dichloroethylene (DCE) and vinyl chloride (VC) as potential bio-product. These compounds have been reported that they can cause clinical diseases and cytotoxicity. However, only a little genotoxic information of these compounds has been known. In this study, we investigated DNA single strand breaks of PCE, TCE, DCE and VC by single cell gel electrophoresis assay, (comet assay) which is a sensitive, reliable and rapid method for DNA single strand breaks with mouse lymphoma L5178Y cells. From these results, $37.5\;{\mu}g/ml$ of PCE, $189\;{\mu}g/ml$ of TCE and $56.4\;{\mu}g/ml$ of DCE were revealed significant DNA damages in the absence of S-9 metabolic activation system meaning direct-acting mutagen. And in the presence of S-9 metabolic activation system, $41.5\;{\mu}g/ml$ of PCE, $328.7\;{\mu}g/ml$ of TCE and $949\;{\mu}g/ml$ of DCE were induced significant DNA damage. In the case of VC, it was revealed a significant DNA damage in the presence of S-9 metabolic activation system. Therefore, we suggest that chloroethylene compounds (PCE, TCE, DCE and VC) may be induced the DNA damage in a mammalian cell.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.74-78
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• 2001

A preparation of water soluble components (EA) was made from carpophores of Elfvingia applanata (Pers.) Karst and its in vitro antiviral activity on vesicular stomatitis virus [(Indiana serotype, VSV(IND)] was investigated by plaque reduction assay. EA exhibited potent antiviral activity on VSV(IND) growth and negligible cytotoxicity on Vero cells, 50% effective concentration ($EC_{50}C$/) of 104$ug\textrm\/ml$ and 50% cytotoxic concentration ($CC_{50}C$) of 3,793$ug\textrm\/ml$, respectively. Selectivity index (Sl $CC_{50}C$/$EC_{50}C$) of EA on Vero cell and VSV(IND) was about 36.5. EA did not display either a direct virucidal effect on V5V(IND) or induction of antiviral substance by Vero cells upon its treatment. Thus, the mode of antiviral activity of EA was studied at steps of viral adsorption onto cell. When both EA and virus were added to cell monolayers, titer of cell-free virus in culture supernatant increased in ca. 30-40% compared with that of control group and titer of cell-associated virus was 60-100% higher than that of control group. These results suggested that antiviral activity of EA on VSV(IND) might be due to the hindrance of viral entry to cells at eITher endocytosis or loss of envelope.

• Journal of Food Hygiene and Safety
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• v.4 no.2
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• pp.109-118
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• 1989

To find antitumor components in the cultured mycelia of Lepiota procera, the proteinpolysaccharide obtained from the mycelia was subjected to DEAE - Sephadex A-50 column chromatography and Sepharose-4B gel filtration. Of the fractions, the purified Fraction C1 was named lepiotan and examined for antitumor activity against the solid form of sarcoma 180 in ICR mice. The inhibition ratio of lepiotan was 64% at the dose of 10 mg/kg/day for 10days. The chemical analysis of lepiotan showed 60% polysaccharide and 21 % protein. The polysaccharide moiety was found to be a heteromannoglucan which consisted of 46.3% glucose, 40.2% mannose and 11.0% fucose. When the antitumor component, Fraction A, was examined for immunopotentiation activity, it was found to increase the number of plaques in hemolytic plaque assay and to restore the immunity in the tumor-bearing mice up to 89.7% of the normal level. Also the antitumor acitivity was suppressed by the treatment with carrageenan, an antimacrophage agent. These results indicate that the antitumor activity was exerted through immunopotentiation, but not through direct cytotoxicity against the tumor.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3363-3368
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• 2014

Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin ($10-60{\mu}M$) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

• Restorative Dentistry and Endodontics
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• v.27 no.5
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• pp.543-551
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• 2002

Nitric oxide (NO) is a small molecule (mol. wt. 30 Da) and oxidative free radical. It is uncharged and can therefore diffuse freely within and between cells across membrane. Such characteristics make it a biologically important messenger in physiologic processes such as neurotransmission and the control of vascular tone. NO is also highly toxic and is known to acts as a mediator of cytotoxicity during host defense. NO is synthesized by nitric oxide synthase (NOS) through L-arginine/nitric oxide pathway which is a dioxygenation process. NO synthesis involves several participants, three co-substrates, five electrons, five co-factors and two prosthetic groups. Under normal condition, low levels of NO are synthesized by type I and III NOS for a short period of time and mediates many physiologic processes. Under condition of oxidant stress, high levels of NO are synthesized by type II NOS and inhibits a variety of metabolic processes and can also cause direct damage to DNA. Such interaction result in cytostasis, energy depletion and ultimately cell death. NO has the potential to interact with a variety of intercellular targets producing diverse array of metabolic effects. It is known that NO is involved in hemodynamic regulation, neurogenic inflammation, re-innervation, management of dentin hypersensitivity on teeth. Under basal condition of pulpal blood flow, NO provides constant vasodilator tone acting against sympathetic vasoconstriction. Substance P, a well known vasodilator, was reported to be mediated partly by NO, while calcitonin-gene related peptide has provided no evidence of its relation with NO. This review describes the roles of NO in dental pulp in addition to the known general roles of it.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.3
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• pp.613-618
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• 2009

Although the effect of Eucommie umoides oliver in osteoporosis has been studied, direct action of Eucommis ulmoides Oliver on osteoclasts remains unknown. Here we examined whether Eucommiae cortex inhibits osteoclast differentiation and bone resorption, a process known to be involved in bone diseases such as osteoporosis. Water extract from Eucommiae cortex (WE-EC) inhibited differentiation of bone marrow macrophages (BMMs) into osteoclasts without causing cytotoxicity. WE-EC suppressed the phosphorylation of p38, ERK, and JNK in BMMs treated with RANKL. WE EC specifically suppressed the mRNA expression of NFATc1 induced by RANKL. However, WE-EC inhibited stability of c-Fos protein induced by RANKL. Furthermore, WE-EC inhibited osteoclast survival induced by RANKL and in turn suppressed bone resorption. Taken together, our results suggest that WE-EC may be better agents for therapeutic use in bone diseases.