• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.95-101
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• 2007

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

• Journal of TMJ Balancing Medicine
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• v.3 no.1
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• pp.15-22
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• 2013

Objectives and Methods: This study was conducted to investigate the formula of ONGABO to composed of Ginseng Radix (Red Ginseng), Angelica Gigantis Radix, Schisandrae Fructus, Cuscuta Semen, Curcumae Tuber with the method to observe the cell viability of HepG2 in the basic principle of oriental medicine formula study, Sovereign, Minister, Assistant and Courier principle (君臣佐使論). Results: Ginseng Radix (Red Ginseng) and Schisandrae Fructus were having a cell protection effect in HepG2 significantly. Angelica gigantis radix was decreased the cell viability of HepG2 significantly, and there were no effects for Cuscuta Semen and Curcumae Tuber to the cell viability of HepG2. Conclusions: As the above results, in the Sovereign, Minister, Assistant and Courier principle (君臣佐使論), Ginseng Radix (Red Ginseng) corresponds to sovereign medicinal having cell protect effects, angelica gigantis radix corresponds to minister medicinal having cell killing effects, Schisandrae Fructus corresponds to assistant medicinal to help red ginseng having cell protect effects. Cuscuta Semen and Curcumae Tuber correspond to courier medicinal having no effect in cell viability in HepG2. We hope the advanced research on sovereign, minister, assistant and courier principle will be proceed in the tomorrow.

• Journal of Nutrition and Health
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• v.37 no.3
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• pp.182-192
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• 2004

Conjugated linoleic acid (CLA) is the mixture of positional and geometric isomers of linoleic acid (LA), which is found abundantly in dairy products and meats. This study was performed to investigate the anticarcinogenic effect of CLA in HepG2 hepatoma cells. HepG2 cell were treated with LA and CLA at the various concentrations of 10, 20, 40, 80 uM each at different incubation times. After each incubation times, cell proliferation, fatty acids incorporation into cell, peroxidation and postaglandin E$_2$ (PGE$_2$) and thromboxane $A_2$ (TXA$_2$) for the eicosanoid metabolism were measured. LA treated HepG2 cells were increased cell growth 6 - 70％ of control whereas CLA increased cell death the half of those in LA group (p 〈 0.001). LA and CLA were incorporated very well into the cellular membranes four times higher than in control according to concentration and longer incubation times. Moreover, LA synthesized significantly arachidonic acids corresponding with LA concentration compared to CLA supplementation. The supplementation with LA increased intracellular lipid peroxides concentration corresponding with LA concentration and five times higher than those in CLA significantly at any incubation times (p 〈 0.001). PGE$_2$ and TXA$_2$ levels were three to twenty times lower in condition of CLA treatments than LA, respectively. Overall, the dietary CLA might change the HepG2 cell growth by the changes of cell composition, production of lipid peroxide. Since CLA have not changed the levels of arachidonic acid of cell membrane, which was sources of eicosanoids, eicosanoid synthesis was not increased in CLA compared to LA. Our results was suggest CLA has a possibility to protect the progress of atherosclerosis because CLA does not produce lipid production and endothelial contraction factors in liver.

• Journal of Ginseng Research
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• v.20 no.3
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• pp.219-225
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• 1996

This study was performed to investigate the inhibition mechanism of cancer cell proof iferation caused by the petroleum-ether extract of ginseng against human rectum (HRT-18), colon (HT-29), llepatoma (Hep G2) and prostate (LNCaP) cancer cells and monkey kidney cells (Vero 76). Cells were treated with the petroleum-ether extract of ginseng (50 to 200 $\mu\textrm{g}$/ml) in G1 or S phase of the cell cycle, and proliferation and protein kinase C activity were measured. The petroleum-eth or extract of ginseng inhibited proliferation of HRT-18, HT-29, Hep G2 and LNCaP when treated in Gl phase, but not in S phase. This result shows that the ginseng extract arrests the cell cycle in G1 phase, resulting in the inhibition of cell proliferation. At the same concentrations, treatment of the ginseng extract in G1 phase decreased protein kinase C activity, while the treatment in S phase had no effect. This reault suggests that protein kinase C might be involved in the inhibition of the cell cycle and proliferation of cancer cells caused by the petroleum-ether extract of ginseng.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.378-384
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• 1999

Retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP) induce the differentiation of the multipotent embryonic carcinoma cell line, F9 cells, into parietal endoderm like cell. The F9 cells are highly proliferative doubling approximately 12 hourse. S Phase is predominant, lasting 10 hours and G2/M phase occupies most of the remaining cycle (2 hours) and G1 phase is nearly non-existent. In this study, we showed the effect of RA and dbcAMPon the cell cycle associated molecules (especially around G1 phase) during F9 cell differentiation. Differentiation of F9 cells was induced by the combined addition of RA ($10^{-7}M$) and dbcAMP (0.5mM), and cells were harvested daily up to 4 days. Flow cytometric analysis showed the prolongation of G1 phase around 30 hours after induction. Western blot analysis revealed that the amount of cyclin D1 and cdk2 were increased at day 4. However, histone H1 kinase activity of cdk2 was decreased. These data strongly suggest that RA and dbcAMP induce the growth arrest of F9 cells at G1 phase by decreasing the activity of cdk2, although they have increased the protein contents of cyclin D1 and cdk2. The reason for the discrepancy between the H1 kinase activity and protein contents are not clear yet.

• KSBB Journal
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• v.9 no.5
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• pp.450-456
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• 1994

The effects of sucrose on cell growth and anticancer drug taxol production were investigated in cell suspension cultures of Taxus cuspidata. The cells were cultured at various concentrations of sucrose (20 to $100g/\ell$). The highest specific growth rata was achieved at $40g/\ell$ of sucrose as 0.076 day-1 and the highest final cell density, 34 g DCW/$\ell$ after 25 days of culture, was obtained at $60g/\ell$ of sucrose. The cell yield(Yx/s) was found to be 0.55g cell/g sucrose and doubling time (Td) was 9.12 day. High concentration of sucrose (80, $100g/\ell$) and the addition of osmoticum enhanced the production of taxol significantly. The maximum taxol production was $1.36mg/\ell$ at $80g/\ell$ of sucrose, which was 0.01% as a specific content.

• Genomics & Informatics
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• v.9 no.4
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• pp.161-172
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• 2011

Angiogenesis is regulated by a large number of molecules and complex signaling mechanisms. The G protein $G{\alpha}_{13}$ is a part of this signaling mechanism as an endothelial cell movement regulator. Gene expression analysis of $G{\alpha}_{13}$ knockout mouse embryos was carried out to identify the role of $G{\alpha}_{13}$ in angiogenesis signaling during embryonic development. Hypoxia-inducible response factors including those acting as regulators of angiogenesis were over expressed, while genes related to the cell cycle, DNA replication, protein modification and cell-cell dissociation were under expressed. Functional annotation and network analysis indicate that $G{\alpha}_{13}{^{-/-}}$ embryonic mice were exposed to hypoxic conditions. The present analysis of the time course highlighted the significantly high levels of disorder in the development of the cardiovascular system. The data suggested that hypoxia-inducible factors including those associated with angiogenesis and abnormalities related to endothelial cell division contributed to the developmental failure of $G{\alpha}_{13}$ knockout mouse embryos.

• The korean journal of orthodontics
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• v.32 no.3 s.92
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• pp.227-234
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• 2002

In order to investigate the action mechanism of protein kinase C on $K^+$ channel in osteoblastic cell, effects of phorbol 12, 13-dibutyrate on human osteoblast-like cells (G292) were studied by patch clamp technique with cell-attacked configuration. 111 this experiment, 45pS ion channel was dominant in G292 cell line according to their approximate conductances in symmetrical 140mM KCl saline at holding potential of 60mV. In torrent-voltage relationship, reversal potential was 5.5mV at the condition of potassium enriched saline in the pipette and -27 mV at the condition of standard extracellular saline In the pipette. Phorbol 12, 13-dibutyrate 10nM increased the open probability of 45pS channel and staurosporine, an inhibitor of protein kinase C, suppressed this effect. Phorbol 12,13-dibutyrate moved the reversal potential of 45pS channel to more negative potential and increased the single channel current at the same membrame potential. In order to check the activation of protein kinase C in G292 cell by phorbol 12,13-dibutyrate, western blot of protein kinase C was performed. Phorbol 12,13-dibutyrate $0.1{\mu}M$ translocated protein kinase C from cellular compartment to membrane compartment of the cell. These findings suggest that phorbol 12,13-dibutyrate, one of phorbol esters, activate 45pS channel In G292 cell and affect cell membrane potential, that regulate cellular function.

• Biomedical Science Letters
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• v.29 no.4
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• pp.287-295
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• 2023

Amifostine was developed to protect cells, but it is known to induce cytotoxicity and apoptosis, and the exact mechanism is unknown. In this study, we investigated how the DNA mismatch repair (MMR) system interacts with p53 to prevent apoptosis, cell cycle arrest, and cytoprotective effects induced by amifostine. HCT116 colon cancer cells sublines HCT116/p53+,HCT116/p53+, HCT116/p53-, HCT116/E6 and HCT116+ch3/E6 cells were used for evaluation. Amifostine induced G1 arrest and increased toxicity two-fold in p53- cells regardless of MMR expression. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Amifostine induced the expression of p21 protein in both p53+ and p53- cells. As for apoptosis, compared to p53- cells, p53+ cells showed 3.5~4.2 times resistance to amifostine-induced apoptosis. HCT116+E6 with both p53 and MMR loss showed maximum apoptosis at 48 h, and HCT116+ch3/E6HCT116+ch3/E6 with p53 loss showed maximum apoptosis at 24 h. As a result, it was confirmed through in vitro experiments that amifostine-induced G1 cell cycle arrest and apoptosis are mediated through a pathway dependent on MMR and p53 protein.

• Environmental Mutagens and Carcinogens
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• v.19 no.1
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• pp.20-27
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• 1999

In order to know the inhibitory effect of magnesium carbonate(MgCO3) on cytotoxicity, DNA damage, mutagenicity, and cell transforming ability of nickel subsulfide, the inhibition of cell proliferation, DNA-protein crosslinks formation (DPC), HGPRT point mutation, and cell transformation were evaluated. Nickel subsulfide(Ni3S2) and magnesium carbonate as insoluble compounds were used for this study. BALB/3T3 cell, CHO-K1 cell, and C3H10T1/2 cell were used in this experiment. Exposure concentration of nickel subsulfide was 1 $\mu\textrm{g}$/ml. The concentrations of magnesium carbonate in this study were 0.6 $\mu\textrm{g}$/ml, 1.2 $\mu\textrm{g}$/ml, 2.4 $\mu\textrm{g}$/ml and the molar ratio of magnesium to nickel when exposed simultanously were 0.5, 1.0 and 2.0 respectively. The results were as follows; 1. Magnesium carbonate reduced the inhibitory effect of nickel subsulfide on cell proliferation. 2. Magnesium carbonate also reduced the effect of nickel subsulfide on DNA-protein crosslinks formation. 3. HGPRT point mutagenicity of nickel subsulfide was reduced when magnesium carbonate treated simultaneously. 4. Magnesium carbonate reduced cell transforming ability of nickel subsulfide. Conclusively, nickel subsulfide showed cytotoxicity, cell transforming ability, and mutagenicity strongly and magnesium carbonate may have protective roles in these nickel effects.