• Journal of Microbiology and Biotechnology
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• v.15 no.3
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• pp.660-664
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• 2005

We have previously isolated specific RNA aptamers with high affinity against the helicase domain of hepatitis C virus (HCV) nonstructural protein 3 (NS3). The RNA aptamers competitively and efficiently inhibited the helicase activity, partially impeding HCV replicon replication in human hepatocarcinoma cells. In this study, the RNA aptamers were tested for binding to the HCV NS3 proteins in eukaryotic cells, using a yeast three-hybrid system. The aptamers were then recognized by the HCV NS3 proteins when expressed in the cells, while the antisense sequences of the aptamers were not. These results suggest that the in vitro selected RNA aptamers can also specifically bind to the target proteins in vivo. Consequently, they could be potentially utilized as anti-HCV lead compounds.

• YAKHAK HOEJI
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• v.49 no.6
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• pp.505-510
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• 2005

Allylthio group of allicin and other organosulfur compounds which are isolated from garlic is considered as a pharmacophore, a key structure component of the molecule which is responsible biological activities. In the foregoing studies various 3-allylthio -6- alkoxypyridazine derivatives (K- compounds ) and 3-allylthio -6- alkylthiopyridazine derivatives(Thio-K-compounds) were synthesized and their biological activities were tested in vivo. They showed good hepatoprotective activities on the carbon tetrachloride-treated mouse and aflatoxin Bl-treated rat and chemopreventive activities on bepatocarcinoma cells in rat as expected. Now 3-allylthio-6-heterocyclylalkylaminopyridazine derivatives that the oxygen atom at 6-Position of 3-allylthio-6-alkoxypyridazine is replaced by nitrogen (N) were synthesiz ed and their activities were tested in vitro against SK-Hep-1 human liver cancer cells. They showed good chemopreventive activities on hepatocarcinoma cells.

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.42.1-42.1
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• 2007

See Full Text

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.43.1-43.1
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• 2007

See Full Text

• Journal of Life Science
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• v.17 no.9 s.89
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• pp.1298-1302
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• 2007

A hallmark of cancers is 'leaky' tight junctions (Tjs). TJs mediated paracellular permeability is elevated and TJs maintained cell polarity is frequently lost. Concomitantly, TJs-associated proteins including members of the claudin family of proteins are dysregulated. Recent findings indicate that these TJs changes can contribute to cancer progression. In this study, we examined the effects of ${\beta}-lapachone$, a quinone compound obtained from the bark of the lapacho tree (Tabebuia avellanedae), on the Tjs-associated regulators in human hepatocarcinoma cell lines, HepG2 and Hep3B. ${\beta}-lapachone$ treatment downregulated the levels of insulin-like growth factor 1 receptor (IGF-lR) proteins in both HepG2 and Hep3B cells. But the levels of claudin-3 and -4 proteins were increased in ${\beta}-lapachone$-treated HepG2 and Hep3B cells. And also the zonnula occludens-l (la-I) and p-catenin protein levels by ${\beta}-lapachone$ were increased in a time-dependent manner. However, claudin-3 and -4 mRNA levels were uninhibited by ${\beta}-lapachone$ in HepG2 and Hep3B. The present results suggest that the upregulation of claudin-3 and -4 protein levels by ${\beta}-lapachone$ occurs by a post-transcriptional mechanism and points to a novel mechanism by ${\beta}-lapachone$.

• Journal of Life Science
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• v.24 no.7
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• pp.769-776
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• 2014

Anisomycin, also known as flagecidin, is an antibiotic produced by Streptomyces griseolus that inhibits protein synthesis by binding to the ribosomal 28S subunit. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptotic cell death. TRAIL primarily causes apoptosis in tumor cells by binding to death receptors. Many human cancer cell lines are refractory to TRAIL-induced cell death. In this study, we investigated whether anisomycin could enhance TRAIL-mediated apoptosis in TRAIL-resistant human hepatocarcinoma Hep3B cells. Treatment with anisomycin and TRAIL alone did not reduce cell viability in Hep3B cells. However, in the presence of TRAIL, the anisomycin concentration dependently reduced the cell viability. Our results indicate that anisomycin sensitizes Hep3B cells to TRAIL-mediated apoptosis and that this occurs, at least partly, via caspase activation. Interestingly, Bid knockdown by small interfering RNA significantly reduced the induction of apoptosis in combination with anisomycin and TRAIL, indicating that anisomycin effectively acts to lower the threshold at which TRAIL-mediated truncated Bid triggers the mitochondrial-mediated apoptosis program in Hep3B cells. Therefore, the use of TRAIL in combination with anisomycin might provide an effective therapeutic strategy for the safe treatment of some TRAIL-resistant cancer cells.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.329-336
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• 2000

Backgrounds : The purpose of this study was to identify drugs that can enhance radioresponse of murine fepatocarcinorna. Methods : CSH/HeJ mice bearing 8 mm tumors of murine fepatocarcinorna, HCa-1, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mghg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21$^{WAF1/CIP1}$. Results :Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gemcitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21$^{WAF1/CIP1}$ Conclusion :Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21$^{WAF1/CIP1}$.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.97-106
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• 2013

Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. HCV core protein plays not only a structural role in the virion morphogenesis by encapsidating a virus RNA genome but also a non-structural role in HCV-induced pathogenesis by blocking innate immunity. Especially, it has been shown to regulate JAK-STAT signaling pathway through its direct interaction with Janus kinase (JAK) via its proline-rich JAK-binding motif ($^{79}{\underline{P}}GY{\underline{P}}WP^{84}$). However, little is known about the physiological significance of this HCV core-JAK association in the context of the virus life cycle. In order to gain an insight, a mutant HCV genome (J6/JFH1-79A82A) was constructed to express the mutant core with a defective JAK-binding motif ($^{79}{\underline{A}}GY{\underline{A}}WP^{84}$) using an HCV genotype 2a infectious clone (J6/JFH1). When this mutant HCV genome was introduced into hepatocarcinoma cells, it was found to be severely impaired in its ability to produce infectious viruses in spite of its robust RNA genome replication. Taken together, all these results suggest an essential requirement of HCV core-JAK protein interaction for efficient production of infectious viruses and the potential of using core-JAK blockers as a new anti-HCV therapy.

• BMB Reports
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• v.48 no.3
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• pp.127-128
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• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

• Journal of Microbiology and Biotechnology
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• v.20 no.4
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• pp.821-827
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• 2010

Gene delivery that provides targeted delivery of therapeutic genes to the cells of a lesion enhances therapeutic efficacy and reduces toxic side effects. This process is especially important in cancer therapy when it is advantageous to avoid unwanted damage to healthy normal cells. Incorporating cancer-specific ligands that recognize receptors overexpressed on cancer cells can increase selective binding and uptake and, as a result, increase targeted transgene expression. In this study, we investigated whether a peptide capable of homing to hepatocellular carcinoma (HCC) could facilitate targeted gene delivery by cationic liposomes. This homing peptide (HBP) exhibited selective binding to a human hepatocarcinoma cell line, HepG2, at a concentration ranging from 5 to 5,000 nM. When conjugated to a cationic liposome, HBP substantially increased cellular internalization of plasmid DNA to increase the transgene expression in HepG2 cells. In addition, there was no significant enhancement in gene transfer detected for other human cell lines tested, including THLE-3, AD293, and MCF-7 cells. Therefore, we demonstrate that HBP provides targeted gene delivery to HCC by cationic liposomes.