Screening of Potential Anticancer Compounds from Marketed Drugs

류광현(Kwang-Hyeon Liu) 한국생명과학회 2011 생명과학회지 Vol.21 No.11

CYP2J2는 치료약물 및 아라키돈산과 같은 내인성 화합물의 대사에 중요한 역할을 수행하고 있는 효소이다. 최근, CYP2J2 단백질이 인체 종양 조직이나 종양 세포주에 과발현되어 있고, CYP2J2 효소의 작용에 의해 생성된 에폭시에이코사트리에논산(EETs)이 세포사멸을 방지한다는 것이 보고되었다. 본 연구는 시판중인 약물 120종을 대상으로 시토크롬 2J2 동종효소에 저해능을 가지는 화합물을 발굴하고자 하였다. 인체 간 마이크로솜 시료에 아스테미졸과 NADPH 재생성계 및 약물(50 μM)을 첨가한 후 15분간 반응시켜 생성된 대사물을 LC/MS/MS를 이용하여 분석하여 시토크롬 2J2 동종효소 활성의 변화를 평가하였다. 그 결과 할로페리돌, 터페나딘, 아리피프라졸, 미코나졸의 순으로 CYP2J2 효소 활성 저해능을 보였다. 미코나졸은 CYP2J2에 의해 매개되는 에바스틴(IC50=11.2 μM) 및 터페나딘(IC50=2.2 μM) 대사를 강력하게 저해하였다. 터페나딘 또한 CYP2J2 매개 에바스틴 대사를 농도 의존적으로 저해하였다(IC50=13.6 μM). 향후, 이들 약물을 대상으로 한 항암 활성 평가가 필요할 것으로 판단된다. Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation (IC50=11.2 μM) and terfenadine hydroxylation (IC50=2.2 μM), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation (IC50=13.6 μM) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.

남성 금연시도자의 타액 내 니코틴 및 코티닌 변화 -대전 서구보건소 등의 금연클리닉 사례

류광현 ( Kwang Hyeon Liu ),황수정 ( Soo Jeong Hwang ) 대한예방치과·구강보건학회 2012 大韓口腔保健學會誌 Vol.36 No.3

Objectives: The Korea Health Promotion Foundation has performed the None-Smoking Project using the Quit-Smoking Clinics in all health care centers. The success rate of quitting smoking in the Quit- Smoking Clinics have run over 40% in the self-reports. The aim of this study was to assess the success rate of quitting smoking using the nicotine and cotinine concentrations in saliva and to find out the factors that influence the success of quitting smoking. Methods: The author collected the data of 122 participants from the Quit-Smoking Clinic in the city of Daejeon and the data 13 nonsmokers as control after their written consent in 2009-2010. Following the initial visit, the unstimulated saliva samples were collcted at the visits after 2 weeks, 2 months, 4 months and 6. The concentrations of nicotine, cotinine, and OH-cotinine were analyzed using the High Performance Liquid Chromatography. The cutoff for the cotinine concentration that distinguished the smokers from nonsmokers was set at 10 ng/ml. Results: The baseline participants who visited the clinic were 84 paritcipants after 2 weeks, 65 after 2 months, 40 after 4 months, and 22 after 6 months. The median concentrations of cotinine (P=0.017) and OH-cotinine (P<0.001) decreased over time. The success rates of quitting smoking were calculated at 32.1% after 2 weeks, 41.5 % after 2 months, 42.5% after 4 months, and 50.0% after 6 months, in the participants who returned to the clinic. The Cotinine level after 2 weeks correlated high-positively to the concentration of that over time (r>0.7). The amount of smoking in a day, the period of smoking, and the total amount of smoking did not correlate to the success of quitting smoking as measured in the cotinine level. Conclusions: In spite of the limitation of the high drop out rate in the participants, it was suggested that the active intervention at 2 weeks could make the success rate of quitting smoking higher, as the cotinine level at 2 weeks correlated to the concentrations after that point very positively.

분광광도계를 이용한 폴리에톡시레이티드 아스코르빈산 분석법 개발

오철학 ( Zhexue Wu ),류광현 ( Kwang-hyeon Liu ) 한국응용생명화학회(구 한국농화학회) 2016 Journal of Applied Biological Chemistry (J. Appl. Vol.59 No.4

본 연구에서는 3-ethyl ascorbic acid를 표준물질로 이용하여, 폴리에톡시레이티드 아스코르빈산의 정량법을 개발하였고, 확립된시험법으로 시중에서 돼지 및 닭의 면역력 증진과 열에 대한 스트레스 경감제로 유통되고 있는 Poustin-C 검체 내 폴리에톡시레이티드 아스코르빈산의 함량 분석을 실제로 분석하여 시험법의 유효성을 검증하였다. 개발한 분석법의 검증은 직선성, 정확성, 정밀성 및 안정성 시험 등을 통하여 평가하였다. 정밀도 시험은 일내 정밀성과 일간 정밀성으로 나누어 확인하였는데, 일내 및 일간 정밀성은 모두 3.4 % 이내로 매우 우수하였다. 그리고 직선성 실험에서는 상관계수(r²)가 0.998 이상으로 우수하였다. 실온에서 6시간까지는 안정하여 실험 도중 분해되지 않음을 확인하였다. 따라서 본 연구에서 개발된 시험법은 검체 내폴리에톡시레이티드 아스코르빈산의 함량을 분석하기 위한 공정 시험법으로 활용할 수 있을 것으로 사료된다. We developed a spectrophotometric assay method for polyethoxylated ascorbic acidusing 3-ethyl ascorbic acid as standard material. The analytical method was validated by linearity, accuracy, precision, and stability. The coefficient of variation of the precision of the assay was less than 3.4 %. The linearity of the calibration curves in the desired concentration range is good (r ² >0.998). 3-Ethyl ascorbic acid and polyethoxylated ascorbic acid were stable in stock solution at room temperature for up to at least 6 h. The developed assay could be used for the content analysis of polyethoxylated ascorbic acid in samples.

Thelephoric acid의 CYP2J2 효소 활성 저해제 평가

오철학(Zhexue Wu),이보람(Boram Lee),송경식(Kyung-Sik Song),류광현(Kwang-Hyeon Liu) 한국생명과학회 2013 생명과학회지 Vol.23 No.9

CYP2J2 효소는 간외의 조직에 존재 하는 효소로써, 주로 심혈관계에 발현되어 있다. CYP2J2는 내인성 대사체 및 여러 치료 약물들의 대사에 중요한 작용을 하고 있다. 또한 CYP2J2는 인체의 종양조직이나 종양 세포주에서 과발현되어 있어, 종양 치료를 위한 새로운 표적이 되고 있다. 본 연구에서는 천연물 10종을 대상으로 시토크롬 2J2 동효소에 저해능을 가지는 화합물을 발굴하고자 하였다. 10종의 천연물 중 thelephoric acid는 CYP2J2에 의해 매개되는 에바스틴(IC50=5.32 μM), 아스테미졸(IC50=3.23 μM) 및 터페나딘(IC50=3.27 μM) 대사를 강력하게 저해하였다. 향후, 이 약물을 대상으로 한 항암 활성 평가가 필요할 것으로 판단된다. Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity (IC50=3.23 μM) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation (IC50=5.32 μM) and terfenadine hydroxylation (IC50=3.27 μM) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

후박(厚朴)과 토후박(土厚朴)의 소장운동에 미치는 영향에 대한 연구

이경진 ( Kyung Jin Lee ),박근용 ( Geun Yong Park ),박규하,류광현 ( Kwang Hyeon Liu ),김태완 ( Tae Wan Kim ),함인혜 ( In Hye Ham ),부영민 ( Young Min Bu ),최호영 ( Ho Young Choi ) 대한본초학회 2011 大韓本草學會誌 Vol.26 No.4

Objectives: Magnoliae officinalis Cortex (MOC) has been used in traditional medicine for digestive diseases in Korea, China and Japan. However, Machili thunbergii Cortex (MTC) also has been used as a substitute of MOC in Korea sometimes. Thus, this study was carried out to investigate and compare the effects of MOC and MTC on intestinal motility of isolated small intestinal segments from ICR mouse. Methods: Changes in motility were recorded via isometric transducers connected to a data acquisition system and amplitude, frequency and area under the curve (AUC) of intestinal spontaneous phasic contraction were compared. Results: The MOC extracts (1~30μg/mL) dose-dependently decreased both amplitudes and frequencies of the spontaneous phasic contraction, but not AUC. However, high concentration of MOC (100 μg/mL) evoked tonic contraction. And it was not inhibited by tetrodotoxin, a sodium channel blocker, and nifedipine, a L-type Ca2+ channel antagonist. These results suggested that MOC (100 μg/mL)-induced tonic contraction is not mediated by nerve or L-type Ca2+ channel. On the other hand, the MTC extracts dose-dependently inhibited amplitude and AUC, but not the frequency. Conclusions:Although both MOC and MTC affected intestinal motility, MOC is more effective on intestinal motility than MTC. And MOC has been used as a traditional medicine for a long time but not MTC. Thus, we suggested that MTC should not be used in Korea as a substitute of MOC and MOC might be useful traditional medicine for gastrointestinal disease. The mechanism of MOC is still remained to elucidate.

포도 중 살충제 Fenitrothion의 잔류 특성

문준관(Joon-Kwan Moon),박희원(Hee-Won Park),최훈(Hoon Choi),홍용순(Yong-Soon Hong),류광현(Kwang-Hyeon Liu),이윤형(Youn-Hyung Lee),이규승(Kyu-Seung Lee),김정한(Jeong-Han Kim) 한국원예학회 2003 Horticulture, Environment, and Biotechnology Vol.44 No.4

The selective induction of leelamine on hepatic CYP 2B activity in ICR mice

Ju Hee Sim(심주희),Woongsik Nam(남웅식),Hungchan O(오흥찬),Suyoun Lee(이수연),Doohyun Lee(이두현),Kwang-Hyeon Liu(류광현),Taeho Lee(이태호),Jae Yun Han(한재윤),Sung Hwan Ki(기성환),Tae Cheon Jeong(정태천),Sangkyu Lee(이상규) 환경독성보건학회 2014 한국독성학회 심포지움 및 학술발표회 Vol.2014 No.5