• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6511-6516
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• 2012

Recently, we reported that an ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. However, the detailed mechanisms were not fully explored. Here, we demonstrate another aspect of the activity of I. nertschinskia in breast cancer cells. We compared the response to an ethanol extract of I. nertschinskia in two different human breast cancer cell lines, Hs578Tand MDA-MB231, respectively with relatively low and high AKT1/2 activity by trypan blue exclusion assay and FACS analysis. Knockdown of endogenous AKT1 or AKT2 in breast cancer cells by RNA interference determined the sensitivity to I. nertschinskia ethanol extract compared to control cells. The I. nertschinskia ethanol extract induced cell death in a manner that depended on the level of phosphorylated AKT1/2 protein and was associated with a significant increase in the sub-G1 cell population, indicative of apoptosis. Our results indicate that an ethanol extract of I. nertschinskia differentially induces cell death in breast cancer cells depending on their level of phosphorylated AKT1/2.

• Korean Journal of Food Science and Technology
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• 제36권4호
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• pp.586-593
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• 2004

Efficient extraction method of crude protein-bound polysaccharide (CPBP) from Agaricus blasei Murill was established. CPBP yields by ultrasonic and hot water extractions were 13.0 and 7.8%, respectively. Pressure extraction for 3 hr gave the highest ${\beta}-glucan$ content; no significant difference was observed between 2 and 3 hr extraction. Four volumes added ethanol gave the highest yields of CPBP and ${\beta}-glucan$ contents at 10.89 and 35.97%, respectively. Decomposition temperature of CPBP was $240-365^{\circ}C$, showing relatively good thermal stability. In SRB (sulforhodamine B) assay, CPBP treatment at $1,000\;{\mu}g/mL$ for 72 hr inhibited proliferations to A549, MCF-7, and AGS cancer cells by 43.9, 21.4, and 32.5%, respectively.

• Korean Journal of Medicinal Crop Science
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• 제16권5호
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• pp.349-355
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• 2008

Anticancer and immuno-modulatory activities of methanol extracts from different parts, bark, wood and leaf, of Cornus macrophylla Wall. were investigated in this study. All extracts at a concentration of 1.0mg/ml showed relativity low cytotoxicities on human normal kidney cell (HEK293) by approximately 25%. Bark extract of C. macrophylla showed the highest anticancer activity on human lung cancer cell line (A549) and human breast cancer cell line (MCF-7) by 57.4% and 58.7%, respectively, at a concentration of 1.0mg/ml. All extracts enhanced the growth of human B and T cells, showing 38.7% and 65.9% increase compared to control, respectively, by 5 days incubation with bark extract. The secretions of interleukin 6 (IL6) and tumor necrosis factor alpha (TNF-$\alpha$) from human B and T cells were significantly increased by extracts, especially bark extract. B or T cell medium, which contains cytokines (IL 6 and TNF-$\alpha$) secreted by bark extract treatment for 5 days, time-dependently enhanced the growth of NK-92MI cells with the maximal effect at 5th day of incubation. These results suggest that C. macrophylla, especially bark, has the potential for anticancer and immuno-modulatory activities.

• Archives of Pharmacal Research
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• 제29권5호
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• pp.354-362
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• 2006

Dietary flavonoids have attracted a great deal of attention as agents for preventing estrogen-related diseases, such as postmenopausal symptoms, and for reducing the risk of estrogen-dependent cancer. Kaempferol is one of the most commonly found dietary phytoestrogen. The aim of this study was to investigate the estrogenic and/or antiestrogenic effect of kaempferol, which can confirm its potency as a preventive agent against estrogen-related diseases. Kaempferol has both estrogenic and antiestrogenic activity, which are biphasic response on estrogen receptor. The estrogenic activity of kaempferol induced via ER-mediated pathway depending on $E_2$ concentration $(\leq\;10^{-12}M)$. Kaempferol $(10^{-5}\;M)$ also caused antiproliferative effect on MCF-7 cell in the presence of $E_2\;(10^{-11}\;M)$ and restored to the addition of excess $E_2\;(10^{-7}\;M)$, which confirms that antiproliferation of kaempferol was induced via ER-dependent pathway. However, at $10^{-4}\;M$, concentration higher than the concentrations at which the estrogenic effects of kaempferol are detected $(10^{-5}\;M)$, kaempferol induced strong antiproliferative effect, but were unaffected by the addition of excess $E_2\;(10^{-7}\;M)$ indicating that kaempferol exerts antiproliferation via ER-independent pathway. In particular, kaempferol blocked the focus formation induced by $E_2$, which confirms that kaempferol might inhibit the malignant transformation caused by estrogens. Therefore, we suggested that kaempferol might regulate a suitable level of estrogenic activity in the body and is expected to have potential beneficial effects in preventing estrogen imbalance diseases (breast cancer, osteoporosis, cardiovascular disease and etc.).

• Journal of the Korean Society of Food Science and Nutrition
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• 제45권6호
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• pp.918-922
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• 2016

The objective of this study was to determine the antioxidant and anti-proliferative activities of methanol, ethanol, acetone, and ethyl acetate extracts from oats (Avena sativa L.). Total polyphenol contents of extracts were analyzed by Folin-Ciocalteu assay. The antioxidant activities of extracts were determined by 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and reducing power. The anti-proliferative activities of colon (HCT116), lung (NCI-H460), and breast (MCF7) cancer cells were investigated. Among solvents, methanol extract showed the highest amount of total polyphenols, which was 8.2 mg gallic acid equivalents/g residue. High levels of ABTS radical [12.1 mg Trolox equivalent antioxidant capacity (TEAC)/g residue] and DPPH radical (4.4 mg TEAC/g residue) scavenging activity and reducing power ($A_{700}=0.39$) were found in methanol extracts. Moreover, methanol extracts indicated higher anti-proliferative activities against HCT116 (69.5%), NCI-H460 (75.2%), and MCF7 (84.8%) cells compared with other extracts. The results show that methanol was the best solvent for extraction of antioxidant and anti-proliferative compounds from oats. Moreover, notable antioxidant and anti-proliferative activities of oats could have significant health benefits.

• Molecules and Cells
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• 제43권3호
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• pp.236-250
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• 2020

Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Up-regulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIP-Br1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikonin-mediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIP-Br1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.

• Journal of Pharmaceutical Investigation
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• 제41권5호
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• pp.301-307
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• 2011

The aim of this study was to investigate the effects of kaempferol on the pharmacokinetics of nimodipine in rats. Nimodipine and kaempferol interact with cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), and the increase in the use of health supplements may result in kaempferol being taken concomitantly with nimodipine as a combination therapy to treat orprevent cardiovascular disease. The effect of kaempferol on P-gp and CYP3A4 activity was evaluated and Pharmacokinetic parameters of nimodipine were determined in rats after an oral (12 mg/kg) and intravenous (3 mg/kg) administration of nimodipine to rats in the presence and absence of kaempferol (0.5, 2.5, and 10 mg/kg). Kaempferol inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of $17.1{\mu}M$. In addition, kaempferol significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Compared to the oral control group, the area under the plasma concentration-time curve ($AUC_{0-\infty}$) and the peak plasma concentration ($C_{max}$) of nimodipine significantly increased, respectively. Consequently, the absolute bioavailability of nimodipine in the presence of kaempferol (2.5 and 10 mg/kg) was 29.1-33.3%, which was significantly enhanced compared to the oral control group (22.3%). Moreover, the relative bioavailability of nimodipine was 1.30- to 1.49-fold greater than that of the control group. The pharmacokinetics of intravenous nimodipine was not affected by kaempferol in contrast to those of oral nimodipine. Kaempferol significantly enhanced the oral bioavailability of nimodipine, which might be mainly due to inhibition of the CYP3A4-mediated metabolism of nimodipine in the small intestine and /or in the liver and to inhibition of the P-gp efflux transporter in the small intestine by kaempferol. The increase in oral bioavailability of nimodipine in the presence of kaempferol should be taken into consideration of potential drug interactions between nimodipine and kaempferol.

• The Korea Journal of Herbology
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• 제36권3호
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• pp.15-24
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• 2021

Objectives : The Glycyrrhiza new varieties, WONGAM and SINWONGAM, were developed through interspecific cross between Glycyrrhiza glabra and Glycyrrhiza uralensis by the National Institute of Horticultural and Herbal Science, Rural Development Administration in Korea. This in vitro study was undertaken to compare the antioxidant and cytotoxic effects between Glycyrrhiza new varieties (WONGAM and SINWONGAM) and official compendia (Glycyrrhiza glabra and Glycyrrhiza uralensis). Methods : Antioxidant activity was determined by DPPH (1,1-diphenyl-2-picrylhy drazyl), ABTS (2,2-azino-bis (3-rthylbenz-thiazoline-6-sulfonic acid)) diammonium salt, Nitrite radical scavenging assay, and Reducing Power assay. Cytotoxicity was determined by MTT assay and cell morphology was observed by an inverted microscope. Results : The DPPH, ABTS, Nitrite radical scavenging activities and reducing power of Glycyrrhiza glabra, Glycyrrhiza uralensis, WONGAM, and SINWONGAM were evaluated at different concentrations (0, 10, 50, 100, 500, 1000 ㎍/㎖). Glycyrrhiza glabra, Glycyrrhiza uralensis, WONGAM, and SINWONGAM showed similar dose-dependent increase in antioxidant activities. The cytotoxic effects with increasing doses of Glycyrrhiza new varieties and official compendia did not differ in HCT116, HT29, A549, MDA-MB231, PC3, ACHN, and HeLa cells. However, significant difference in cytotoxicity were observed in AGS, MCF7 and Hep3B cells by Glycyrrhiza glabra, Glycyrrhiza uralensis, WONGAM, and SINWONGAM. Conclusions : These results showed that Glycyrrhiza new varieties and official compendia acts as a potent antioxidant. Also, the finding that equivalent cytotoxic potency was observed in a cell dependent manner. Our study suggests that Glycyrrhiza new varieties may offer a wide-variety of health benefits.

• Korean Journal of Food Science and Technology
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• 제45권5호
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• pp.619-627
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• 2013

We investigated the characteristics and biological activity of makgeolli supplemented with different levels (0%, 1%, 3%, 5%, and 7%) of Akebia quinata fruit during fermentation. Our results showed that supplementation with Akebia quinata fruit led to an increase in the acidity level, amino acid concentration, alcohol content, and total sugar level. Makgeolli supplemented with 7% Akebia quinata fruit showed the highest total sensory score. Supplementation with Akebia quinata fruit resulted in a significant increase in the antioxidant activity and nitric oxide inhibitory activity. Further, makgeolli supplemented with Akebia quinata fruit showed anticancer activity against DU145, HeLa, MCF-7, and U87cells, and significantly enhanced antibacterial activity against Shigella flexneri. Our results indicate that Akebia quinata fruit represents an effective natural additive for enhancing the biological activities of makgeolli.

• YAKHAK HOEJI
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• 제54권4호
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• pp.252-257
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• 2010

The aim of this study was to investigate the effect of resveratrol on the pharmacokinetics of nifedipine in rats. The pharmacokinetic parameters of nifedipine were measured after the oral administration of nifenipine (6 mg/kg) in the presence or absence of resveratrol (0.5, 2.5 and 10 mg/kg, respectively). The effect of resveratrol on the P-glycoprotein (Pgp), CYP 3A4 activity was also evaluated. Resveratrol inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 0.94 ${\mu}M$. In addition, resveratrol significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. Compared to the control groups, the presence of 2.5 mg/kg and 10 mg/kg of resveratrol significantly (p<0.05, p<0.01) increased the area under the plasma concentrationtime curve (AUC) of nifedipine by 49~75%, and the peak concentration ($C_{max}$) of nifedipine by 48~66%. The absolute bioavailability (AB%) of nifedipine was significantly (p<0.05) increased by 22.9-34.8% compared to the control (19.8%). The terminal half-life ($T_{1/2}$) of nifedipine was significantly (p<0.05) increased compared to the control. While there was no significant change in the time to reach the peak plasma concentration ($T_{max}$) of nifedipine in the presence of resveratrol. It might be suggested that resveratrol altered disposition of nifedipine by inhibition of both the CYP3A and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of resveratrol significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of resveratrol or resveratrol-containing dietary supplenment with nifedipine should require close monitoring for potential drug interation.