비소화합물에 의한 A549 폐암세포의 증식억제에 관한 연구

최영현(Yung Hyun Choi),최우영(Woo Young Choi),최병태(Byung Tae Choi),이용태(Yong Tae Lee),이원호(Won Ho Lee) 한의병리학회 2005 동의생리병리학회지 Vol.19 No.4

불임 ICR 수컷 Mouse의 염색체 조기분리 및 정소의 조직학적 성상

최영현(Yung Hyun Choi),최병태(Byung Tae Choi),조운복(Un Bock Jo),이원호(Won Ho Lee) 한국실험동물학회 1994 Laboratory Animal Research Vol.10 No.1

β - Sitosterol에 의한 인체 대장암 HCT116 세포의 증식억제에 관한 연구

최영현(Yung Hyun Choi),김영애(Young-Ae Kim),박철(Cheol Park),최병태(Byung Tae Choi),이원호(Won Ho Lee),황경미(Kyung-Mi Hwang),정근옥(Keun-Ok Jung),박건영(Kun-Young Park) 한국식품영양과학회 2004 한국식품영양과학회지 Vol.33 No.1

β-Sitosterol은 과일과 야채 등을 포함한 대부분의 고등식물에 존재하는 중요한 phytosterol의 하나로서, 인체 암의 예방과 치료에 매우 유효한 것으로 보고되어져 오고 있다. 본 연구에서는 β-sitosterol의 암세포 증식억제 기전의 해석을 시도하기 위하여 인체 대장암세포 HCT116의 증식에 미치는 β-sitosterol의 영향을 조사하였다. β-Sitosterol의 처리로 HCT116 암세포의 증식은 처리 농도 의존적으로 감소되었으며, 특히 7.5 μM 이상 처리에서는 급격한 성장억제 효과가 있었다. 또한 5.0 μM 처리군에서부터 apoptotic body의 형성이 관찰되었고, β-catenin 단백질의 분해 현상과 연관성이 있었다. 그리고 β-sitosterol이 처리된 암세포에서는 종양억제 유전자 p53 및 Cdk inhibitor p21의 발현이 전사 및 번역 수준에서 모두 증가되었다. 본 결과는 그동안 연구가 거의 진행되어져 있지 않았던 β-sitosterol에 의한 암세포주기 조절 해석을 위한 주요한 자료로 활용될 것이다. β-Sitosterol is the major phytosterol in higher plants, including fruits and vegetables. The molecule has been shown to have the potential for prevention and therapy for human cancer. We investigated the effects of β-sitosterol on the cell proliferation of HCT116 human colon cancer cells in order to understand its anti-proliferative mechanism. β-Sitosterol treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. The anti-proliferative effect of HCT116 cells by β-sitosterol was associated with formation of apoptotic bodies and degradation of β-catenin protein. In addition, β-sitosterol-treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 without alteration in the levels of cyclins and Cdks. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of β-sitosterol.

어성초즙 및 추출물의 항돌연변이 효과

최영현(Yung-Hyun Choi),김은영(Eun-Young Kim),박건영(Kun-Young Park),이숙희(Sook-Hee Rhee),이원호(Won-Ho Lee) 한국식품영양과학회 1994 한국식품영양과학회지 Vol.23 No.6

본 연구는 녹황색 채소류에서 항암 및 항돌연변이물질 탐색 작업의 일환으로 어성초 추출물 중 활성의 정도가 비교적 높게 나왔던 즙액과 가열액의 항돌연변이 효과를 Salmonella와 Drosophila를 이용한 in vitro 및 in vivo 돌연변이 검출계를 사용하여 비교 조사하였다. 생어성초 즙액과 건조어성초 가열액을 추출하여 Salmonella typhimurium TA98과 TA100에서 aflatoxin B₁에 대한 항돌연변이성을 실험한 결과, 어성초 즙액은 농도 증가에 따라 저해효과가 76%에서 98%로 증가했으며, 가열액은 86~97%의 저해효과를 나타내었다. N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)에 대한 시료 즙액과 가열액의 항돌연변이 효과를 검토한 결과, 즙액은 농도증가에 관계없이 저해효과가 52~60%로 비슷하게 나타났으나, 가열액의 저해효과는 비교적 낮게 (24~35%) 나타났다. D. melanogaster의 mwh/ + 검출계에서도 두 종류의 어성초 추출물이 MNNG에 의한 유전자 돌연변이나 결실, 염색채 재조 환등의 유발에 억제효과가 있는 것으로 관찰되었다. The inhibitory effects of the juice and boiling water extract of Houttuynia cordata Thunb., which has been known as a traditional folk antitumor agent, on the genotoxicity induced by mutagens were investigated. For this purpose, Salmonella typhimurium TA98 and TA100, and the transheterozygous(mwh/+) third larvae of Drosophila melanogaster were used. The juice of fresh H. cordata (JHC) and boiling H. cordata extract (BHC) showed antimutagenicities toward aflatoxin B₁ in S. typhimurium TA98 and TA100. The JHC's inhibitory effect increased by 76% to 98% as the adding concentrations increased, and the BHC had a 86~97% inhibitory effect. However, in the case of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the JHC's inhibitory effect was 52~60% irrespective of its concentrations and the BHC had a low inhibitory effect. The JHC and BHC slightly reduced the somatic chromosomal mutagenicity by MNNG in the wing hair spot test system (mwh/+) of D. melanogaster, which suggests that they can inhibit gene mutation, deletion and mitotic chromosomal recombination.

Drosophila에서 인삼 및 단삼 추출물이 MNNG의 돌연변이원성에 미치는 영향

최영현(Yung Hyun Choi),정해영(Hae Young Chung),유미애(Mi Ae Yoo),이원호(Won Ho Lee) 대한약학회 1994 약학회지 Vol.38 No.3

Using germinal and somatic cell mutation assaying systems of Drosophila melanogaster, effects of Ginseng and Salvia miltiorrhiza extracts on the in vivo mutagenicity induced by N-methyl-N''-nitro-N-nitrosoguanidine(MNNG) were investigated. For these purpose, the attached-X method and the mwh/flr spot test system which are an X-linked lethal mutation and a somatic chromosome mutation assaying system, respectively, were used. In the induction of X-linked lethal mutations during the spermatogenesis, MNNG showed more actions in the sperm and spermatid stages, in which Ginseng and Salvia miltiorrhiza extracts had remarkable inhibitory effects than other stages. Ginseng and Salvia miltiorrhiza extracts reduced the mutagenicity by MNNG in the mwh/flr system, which reveal that they can inhibit gene mutation, deletion and mitotic chromosomal recombination. These results seem to suggest that Ginseng and Salvia miltiorrhiza extracts may exert their inhibitory effects to in vivo mutagenic and/or carcinogenic properties of DNA-damaging agents.

Drosophila melanogaster 에 미치는 Kojic acid 의 독성에 관한 연구

최영현,박연규,이원호 ( Yung Hyun Choi,Yeon Kyu Park,Won Ho Lee ) 한국환경생물학회 1996 환경생물 : 환경생물학회지 Vol.14 No.1

The present experiment was carried out to detect the basic toxic effect of kojic acid (5-hydroxy-2-hydroxymethyl-γ-pyrone), a fungal metabolite produced by some species of Aspergillus and Penicillium, in Drosophila melanogaster. Kojic add was highly toxic on the developmental and adult stages, resulting in prolongation of the developmental time and lowering of the viability from larvae to adult, and high mortality of adults as dose increased. The LC_50 value at 72 hr i.e., the concentration at which 50% of treated flies died within 72hr, was about 4.8㎎/㎖. As to the sex ratio of flies fed kojic acid during the development, there was no differences between the control and the treated groups. And, kojic acid gave no a significant mutagenic effect on the induction of the sex-linked lethal mutagenesis by the attached-X method used in this study.

인체백혈병세포의 증식에 미치는 불등가사리 메탄올 추출물의 영향

최우영,김기영,이원호,배송자,최영현,Choi, Woo Young,Park, Cheol,Kim, Gi Young,Lee, Won Ho,Bae, Song-Ja,Choi, Yung Hyun 한국해양바이오학회 2006 한국해양바이오학회지 Vol.1 No.2

본 연구에서는 다양한 인체암세포의 증식에 미치는 등불가사리 메탄올 추출물(MEGF)의 영향을 조사하였다. MEGF는 처리 농도의존적으로 암세포의 형태적변이 및 증식억제가 효과를 보여주었으며, 특히 백혈병세포에서 가장 높은 감수성을 보여주었다. 따라서 백혈병세포의 증식억제 효과가 apoptosis 유발과 연관성이 있는지를 flow cytometry 분석 및 DAPI staining 법으로 조사한 결과, MEGF 처리에 의한 백혈병세포의 증식억제는 세포주기 교란과 무관한 apoptosis 유발에 의한 것임을 sub-G1기 세포의 빈도 증가 및 apoptotic body 형성의 증가 등으로 확인하였다. 또한 MEGF 처리에 의한 백혈병세포의 증식억제 및 apoptosis 유발은 p53 비의존적인 p21의 발현 증가 및 Fas/FasL system의 발현 증가와 연관성이 있음을 알 수 있었다. 이상의 결과들은 인체 암세포, 특히 백혈병세포에서 MEGF의 항암작용을 이해하는데 중요한 자료가 될 것이고 나아가 MEGF 내 함유된 생리활성 물질의 분리 및 항암적용 연구를 위한 중요한 기초 자료로 활용될 것이다. Epidemiological studies have indicated that the ubiquitous consumption of seaweeds is a protective factor against some types of cancer. Previous results showed that the administration of seaweed powder or extract reduced the incidence rate of chemically induced tumorigenesis using in vivo animal model. Recently, we reported that the extracts of Gloiopeltis furcata, a kind of Korean edible seaweed, caused he cell growth inhibition of various human cancer cell lines, among them methanol extract exhibited a relatively strong antiproliferative activity. However, the molecular mechanisms of this seaweed in malignant cells have been poorly studied until now. To elucidate this problem, we investigated the effects of methanol extract of G. furcata (MEGF) on the growth inhibition in several human cancer cell lines, and further we analyzed the effects of this extract were tested on the activity of apoptosis induction in human leukemic cells. The results demonstrated that MEGF treatment resulted in the morphological changes and the growth inhibition in a dose-dependent manner. Furthermore, MEGF potently suppresses the growth of human leukemic U937 cells by induction of apoptosis, which was associated with induction of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in a tumor suppressor p53-independent fashion and up-regulation of Fas/FasL system. Further studies will be needed to identify the active compounds that confer the anticancer activity of MEGF. Once such compounds are identified, the mechanisms by which they exert their effects can begin to be characterized.

Drosophila melanogaster 에 미치는 DDVP 의 생리변이적 영향에 관한 연구

최영현,박연규,이원호 ( Yung Hyun Choi,Yeon Kyu Park,Won Ho Lee ) 한국환경생물학회 1994 환경생물 : 환경생물학회지 Vol.12 No.2

DDVP(dichlorvos, 2, 2-dichlorovinyl dimethyl phosphate), the organophoso phorus pesticide, was fed to the Drosophila melanogaster complex in order to investigate its toxic capacity at development of D. melanogaster larvae and four species adults of the D. melanogaster complex(D. mauritiana, D. simulans, D. mauritiana, and D. sechellia). And the potency of DDVP for the induction of the X-linked lethal and somatic chromosomal mutations of D. melanogaster was studied. For these purposes, an attached-X method for germinal cell level and a wing hairs spot test system(mwh/flr system) for somatic cell level were appllied. DDVP was highly toxic on the development of D. melanogaster, resulting in of lowering the viability and in prolongation of the developmental time. The order of mortality causing adult stage feeding to DDVP in the D. melanogaster complex was like this; D. simulans, D. mauritiana, D. sechellia and D. melanogaster. The effect on the sex-linked lethal mutagenesis using an attached-X method was found to be negative. But the frequency of small single mwh spots due to terminal deletion or gene mutation on chromosome 3 in the transheterozygouse(mwh +/+ flr) larvae treated with DDVP were slightly higher than the control group.

Drosophila melanogaster 에 미치는 제초제의 생리변이적 영향에 관한 연구

최영현,박연규,유미애,이원호 ( Yung Hyun Choi,Yeon Kyu Park,Mi Ae Yoo,Won Ho Lee ) 한국환경생물학회 1996 환경생물 : 환경생물학회지 Vol.14 No.2

Glyphosate (isopropylamine salt of N-(phosphono methyl)) and glufosinate ammonium (ammonium 4-[hydroxy(methyl) phosphinoyl]), the herbicides, were fed to Drosophila melanogaster in order to compare their physiological toxic and mutagenic effects. These herbicides were highly toxic on the development of D. melanogaster, resulting in lowering the viabilities from larvae to adults and prolongation of the developmental times, and glufosinate ammonium was slightly more toxic than glyphosate. As to the sex ratio of adult flies fed these herbicides during the development, there was no differences between the control and the treated groups. We also tested the somatic cell mutageneic potencies of these herbicies using a Drosophila wing hairs spot test system (mwh/flr system). The frequencies of small single mwh spots due to terminal deletion or gene mutation on chromosome 3 in the transheterozygouse (mwh +/ + flr) larvae treated with these herbicies were 3∼4 times higher than those of the control group. These results seem to suggest that glyphosate and glufosinate ammonium may exert their mutagenic properties.

마늘 열수 추출물의 활성산소종 생성을 통한 인체백혈병세포의 apoptosis 유발

최우영(Woo Young Choi),정경태(Kyung Tae Chung),윤태경(Tae Kyung Yoon),최병태(Byung Tae Choi),이용태(Yong Tae Lee),이원호(Won Ho Lee),류충호(Chung Ho Ryu),최영현(Yung Hyun Choi) 한국생명과학회 2007 생명과학회지 Vol.17 No.12

본 연구에서는 몇 가지 암세포를 대상으로 마늘 열수추출물(WEAS)의 항암활성을 조사하였으며, 비교적 높은 감수성을 보인 백혈병세포를 대상으로 세포증식억제가 apoptosis 유도와 연관성이 있음을 제시하였다. WEAS에 의한 U937 세포의 apoptosis 유도는 세포주기 G2/M arrest와 연관성이 있었으며, 다양한 apoptosis 조절 유전자들의 발현 변화를 동반하였음을 확인하였다. 이러한 apoptosis 조절 인자들의 발현변화는 미토콘드리아 막 전위의 소실과 연관성이 있었으며, WEAS에 의한 암세포의 G2/M arrest에 의한 apoptosis 유발에 ROS가 중요한 조절자로 작용함을 알 수 있었다. The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protectionagainst WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion,the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.