• BMB Reports
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• v.46 no.12
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• pp.611-616
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• 2013

Luteolin-7-O-glucoside (LUT7G), a flavone subclass of flavonoids, has been found to increase anti-oxidant and anti-inflammatory activity, as well as cytotoxic effects. However, the mechanism of how LUT7G induces apoptosis and regulates cell cycles remains poorly understood. In this study, we examined the effects of LUT7G on the growth inhibition of tumors, cell cycle arrest, induction of ROS generation, and the involved signaling pathway in human hepatocarcinoma HepG2 cells. The proliferation of HepG2 cells was decreased by LUT7G in a dose-dependent manner. The growth inhibition was due primarily to the G2/M phase arrest and ROS generation. Moreover, the phosphorylation of JNK was increased by LUT7G. These results suggest that the anti-proliferative effect of LUT7G on HepG2 is associated with G2/M phase cell cycle arrest by JNK activation.

• Journal of Cancer Prevention
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• v.23 no.4
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• pp.170-175
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• 2018

Background: Human hepatocellular carcinoma (HCC) is a common liver tumor and the main cause of cancer-related death. Tyrosine kinase inhibitors, such as imatinib and GNF5 which were developed to treat chronic myelogenous leukemia, regulate the progression of various cancers. The aim of this study was to confirm the anti-tumor activity of tyrosine kinase inhibitors through regulation of S-phase kinase-associated protein 2 (Skp2), an important oncogenic factor in various cancer cells, in human hepatocarcinoma SK-HEP1 cells. Methods: Cell viability and colony formation assays were conducted to evaluate the effects of imatinib, GNF5 and GNF2 on the growth of SK-HEP1 cells. Using immunoblot analysis, we assessed change of the activation of caspases, PARP, Akt, mitogen-activated protein kinases, and Skp2/p27/p21 pathway by imatinib and GNF5 in SK-HEP1 cells. Using sh-Skp2 HCC cells, the role of Skp2 in the effects of imatinib and GNF5 was evaluated. Results: Imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells. Treatment of imatinib and GNF5 decreased Skp2 expression and Akt phosphorylation, and increased the expression of p27, p21, and active-caspases in SK-HEP1 cells. In sh-Skp2 HCC cells, cell growth and the expression of Skp2 were inhibited by more than in the mock group treated with imatinib and GNF5. Conclusions: These results suggest that the anti-growth activity of tyrosine kinase inhibitors may be associated with the regulation of p27/p21 and caspases through Skp2 blockage in HCC cells.

• Journal of Microbiology and Biotechnology
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• v.18 no.11
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• pp.1862-1867
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• 2008

Streptochlorin is a small molecule isolated from marine Streptomyces sp. that is known to have antiangiogenic and anticancer properties. In this study, we examined the effects of this compound on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death, using a human hepatocarcinoma Hep3B cell line. The results of this study demonstrated that streptochlorin mediates ROS production, and that this mediation is followed by a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\Psi}_m$), activation of caspase-3, and downregulation of antiapoptotic Bcl-2 protein. The quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the streptochlorin-induced apoptosis effects via inhibition of ROS production, MMP collapse, and the subsequent activation of caspase-3. These observations clearly indicate that ROS are involved in the early molecular events in the streptochlorin-induced apoptotic pathway. Taken together, our data imply that streptochlorin-induced ROS is a key mediator of MMP collapse, which leads to the caspase-3 activation, culminating in apoptosis.

• 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 ${\beta}-lapachone$.

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.98.2-98.2
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• 2008

• 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 Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1250-1255
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• 2008

Onchungeum(OCE), a herbal formula, has been used for treatment of anemia, discharging blood and skin diseases. In the previous study, we investigated the anti-cancer effect of OCE by G1 arrest of the cell cycle in human hepatocarcinoma cells, Hep3B cells. In this study, it was examined that the difference of anti-proliferative mechanisms by change in the ratio of OCE composition (OCE I) in Hep3B cells. Treatment of OCE I exhibited a relatively strong anti-proliferative activity and caused various morphological changes such as membrane shrinkage and cell floating. In addition, OCE-I arrests the cell cycle at G1 phase, which was associated with the down-regulation of cyclin D1 and Cdk6 expressions. The G1 arrest was also associated with the induction of Cdk inhibitors p27 and p21. Moreover, both p21 and p27 were detected by immunoprecipitation with anti-Cdk4 and anti-Cdk2 antibodies in OCE I-treated cells but in case of OCE, p21 did not make any complexes with Cdk4 and Cdk2. These results suggest that the change in the ratio of OCE composition might induce different mechanisms in anti-cancer efficacy of OCE, which may confer characteristic principles in oriental medical formula.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2375-2380
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• 2014

In the present investigation, a series of some novel 1,3-diaryl/heteroarylprop-2-en-1-one derivatives (3a-j) have been synthesized and evaluated for their in vitro cytotoxicity against three cancer cell lines, two hepatocarcinoma cell lines HUH-7, Hep-3b and one leukemia cancer cell line MOLT-4. Based on these results, structure-activity relationship (SAR) was studied on modification of $R^1$ and $R^2$ to identify the compound with maximum potency. Amongst the compounds, 3b and 3d strongly inhibited the growth of Hep-3b and MOLT-4 cells with $IC_{50}$ value of 3.39 and $3.63{\mu}M$ respectively. The results obtained from the inhibitory study had further been supported by the reactive oxygen species (ROS) measurement using flow cytometry in MOLT-4 cells. These observations collectively reveal that compounds comprising 1,3-diarylprop-2-en-1-one framework with pyrazole ring at position-3 and heteroaryl/aryl substituents at position-1 can be used as promising anticancer agents.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.519-526
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• 2012

Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. It is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.