• BMB Reports
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• 제53권12호
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• pp.628-633
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• 2020

WNT11 is a member of the non-canonical Wnt family and plays a crucial role in tumor progression. However, the regulatory mechanisms underlying WNT11 expression are unclear. Tumor necrosis factor-alpha (TNFα) is a major inflammatory cytokine produced in the tumor microenvironment and contributes to processes associated with tumor progression, such as tumor invasion and metastasis. By using site-directed mutagenesis and introducing a serial deletion in the 5'-regulatory region of WNT11, we observed that TNFα activates the early growth response 1 (EGR1)-binding sequence (EBS) in the proximal region of WNT11 and that the transcription factor EGR1 is necessary for the TNFα-induced transcription of WNT11. EGR1 bound directly to the EBSs within the proximal 5'-regulatory region of WNT11 and ectopic expression of EGR1 stimulated WNT11 promoter activity, whereas the knockdown of EGR1 expression by RNA interference reduced TNFα-induced WNT11 expression in T47D breast cancer cells. We also observed that mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase mediated TNFα-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNFα stimulation in breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.179-184
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• 2014

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

• 생약학회지
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• 제47권1호
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• pp.7-11
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• 2016

The aerial part of Trichosanthes kirilowii Maxim. (Cucurbitaceae), has long been used in traditional Korean and Chinese medicines for the treatment of heatstroke. We isolated and identified three flavones, luteolin-7-O-${\beta}$-D-glucopyranoside(1), luteolin-4'-O-${\beta}$-D-glucopyranoside(2), luteolin(3) from its methanolic extract. In the present study, we found that luteolin attenuates the lipopolysaccharide(LPS)-induced inflammation in BV2 microglial cells. Luteolin significantly inhibited LPS-induced production of pro-inflammatory mediators such as nitric oxide(NO) and prostaglandin $E_2(PGE_2)$ in BV2 microglia in a concentration-dependent manner without cytotoxic effect. Luteolin dose-dependently suppressed the protein expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2). In addition, luteolin also showed significant induction of heme oxygenase(HO)-1. These results suggest that both the aerial part of T. kirilowii and luteolin may be good candidates to regulate LPS-induced inflammatory response.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.83-83
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• 2003

The lutropin/choriogonadotropin receptor (LHR) is a member of the rhodopsin-like subfamily of G protein coupled receptor (GPCRs), that has been shown to mediate the internalization of its two naturally occurring agonist, lutropin and choriogonadotropin (CG). The clustered agonist-receptor complex is internalized by a dynamin-dependent pathway and traverses the endosomal compartment without agonist dissociation Dissociation of the agonist-receptor complex occurs in the lysosomes, where both the agonist and receptor are degrade. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty (FMPP). A FMPP is a form of sexual precocious puberty in boys in which testosterone levels are elevated independent of changes in luteinizing hormone-releasing hormone and serum luteinizing hormone levels, We have now analyzed two naturally occurring, constitutively active mutants of the human LHR. These mutations were introduced into the rat LHR (rLHR) and are designated L435R and D556Y. Cells expressing rLHR-D556Y bind human choriogonadotropin (hCG) with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. Cells expressing rLHR-L435R also bind hCG with normal affinity, exhibit a 47-fold increase in basal cAMP, and do not respond to hCG with a further increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17- fold, respectively We conclude that the state of activation of the rLHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing rLHR-L435R is due to the fast rate of internalization of the bound hCG. The finding that membranes expressing rLHR-L435R respond to hCG with an increase in adenylyl cyclase activity supports this suggestion. Autonomous Leydig cell activity in FMPP is caused by a constitutively activating LH/CGR.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5785-5790
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• 2012

The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

• 생명과학회지
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• 제9권4호
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• pp.395-407
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• 1999

The queens of Korean native bumblebee species, Bombus ignitus were collected from the field in the spring of 1997 and reared under the various temperatures as 15$^{\circ}C$$\pm$1$^{\circ}C$, 2$0^{\circ}C$$\pm$1$^{\circ}C$, $25^{\circ}C$ $\pm$1$^{\circ}C$, 3$0^{\circ}C$$\pm$1$^{\circ}C$, 60%$\pm$5% of relative humidity and 14L : 10D, to investigate their ecological characteristics, as comparing with control(29$^{\circ}C$$\pm$1$^{\circ}C$, 60%$\pm$5% of relative humidity and red light). As a result, eggs were laid by foundation queen at 15$^{\circ}C$, but they didn't hatched out while at 2$0^{\circ}C$ eggs were laid by them and they hatched out. When a foundation queen laid eggs at $25^{\circ}C$ and they all were hatched out and normally grown. Finally they were developed to the normal colony. B. ignitus worker survived for 77days at 2$0^{\circ}C$, about 69days at $25^{\circ}C$, about 68days at 3$0^{\circ}C$ and about 63days at 29$^{\circ}C$(control). The first brood workers emerged in 25-27days from the egg which a foundation queen laid. At the various temperatures, the captive queens stand to lay eggs in about 18days at 15$^{\circ}C$, 15days at 2$0^{\circ}C$, 11days at $25^{\circ}C$, 11days at 3$0^{\circ}C$ and 4days in control. The first worker and the first drone from the egg cell of the collected queens appeared in about 27days and 72days at 2$0^{\circ}C$, 26days and 88days in $25^{\circ}C$, 24days and 65days at 3$0^{\circ}C$, 25days and 71days in control, respectively. In colony foundation, 33% of the collected queen at 2$0^{\circ}C$ and $25^{\circ}C$, 100% of the disposed queen at 3$0^{\circ}C$ and in control, and 67% of them at 3$0^{\circ}C$ and in control both produced new queens in 66days and 88days, respectively. The life span of the colony founded covered fro about 3 months at $25^{\circ}C$, 3$0^{\circ}C$ and in control. At lower temperatures, the life span of queen is shorter; 2 months at 15$^{\circ}C$ and 3 months at 2$0^{\circ}C$, respectively. A colony which normally developed, varied in size with rearing temperatures; about 20heads at 2$0^{\circ}C$, 482heads at $25^{\circ}C$, 330heads at 3$0^{\circ}C$ and 452heads in control. A foundation queen monthly oviposited 1.5egg cells at 15$^{\circ}C$, 3.0egg cells at 2 $0^{\circ}C$, 21.7egg cells at $25^{\circ}C$, 42.3egg cells at 3$0^{\circ}C$ and 47.0egg cells in control. As a colony developed in June and July, egg cells as well as daily average cells increased in number, as compared to those in May and August. Also, in June and July, interval(days) of egg laying is shorter than in May and August. Number of nectar pots during the colony development varied with rearing temperatures; 31pots at $25^{\circ}C$, 39pots at 3$0^{\circ}C$, 23pots in control. The emergence of new queen showed a distinctively different two patterns; early emerging type and late emerging type. Workers are rapidly increased from early in July to early in August at $25^{\circ}C$, but at 3$0^{\circ}C$ and in control, emergence of workers are remarkably increased from the middle of June and last until July. No new queen emerged at 15$^{\circ}C$, 2$0^{\circ}C$ and $25^{\circ}C$. New queens at 3$0^{\circ}C$ and in control emerged between late in June and early in July. Thus emergence of new queen was temperature dependent.