천궁이 Phase II 효소 유도와 Ornithine Decarboxylase 활성에 미치는 영향

손윤희,김미경,조현정,남경수,Shon, Yun-Hee,Kim, Mee-Kyung,Cho, Hyun-Jung,Nam, Kyung-Soo 대한동의생리학회 2006 동의생리병리학회지 Vol.20 No.6

Water extract from Cnidii Rhizoma (CRW) was tested for colon cancer chemopreventive activity by measuring the induction of phase II detoxification enzyme activity [quinone reductase (QR) and glutathione S-transferase (GST)] and glutathion (GSH) levels and ornithine decarboxylase (ODC) activity in cultured human colorectal adenocarcinoma HT-29 cells. CRW inhibited cell proliferation in cultured HT-29 cells. CRW induced QR activity in a dose-dependent manner in a concentration range of 0.1${\sim}$5.0 $mg/m{\ell}$. GST activity was also induced with the treatment of CRW in HT-29 cells. In addition GSH levels was increased with CRW. CRW inhibited ODC activity, a key enzyme of polyamine biosynthesis, which is enhanced in tumor promotion. These results suggest that CRW has colon cancer chemopreventive activity by increasing phase II enzyme activity and GSH levels and inhibiting ODC activity in vitro.

Ames 및 umu assay를 이용한 감궁탕의 안전성평가

손윤희,김철호,남경수,Shon Yun Hee,Kim Cheorl Ho,Nam Kyung Soo 한국생명과학회 2005 생명과학회지 Vol.15 No.2

감궁탕의 돌연변이원성을 유무를 알아보기 위해 Salmonella typhimurium TA 98 및 TA100을 이용한 돌연변이 원성 실험에서도 감궁탕은 어느 균에서도 돌연변이원성을 나타내지 않았으며, 이는 S-9 mixture 의해 감궁탕이 대사가 된 후에도 이와 유사한 경향을 나타내었다. 또한, SOS umu test의 경우에서도 $\beta-galactosidase$활성에는 별다른 영향을 미치지 않는 것으로 보아 감궁탕은 돌연변이원성을 일으키지 않는 것으로 판정되었으며 S-9 mixture처리에 의한 대사 후에도 이와 유사한 실험결과가 나타났다. 따라서 감궁탕은 그 자체 및 대사 후에도 DNA에 별다른 영향을 미치지 못하는 비교적 안전한 생약처방으로 여겨진다. Gamgung-tang (GGT) that is included in Gamdu-tang (consists of Glycyrrhizae Radix, black beans) and Gunggui-tang(consists of Angelicae Radix and Cnidii Rhizoma) showed therapeutic effect of autoimmume thyroiditis in the previous reports. GGT was tested for the safety using Ames and umu gene expression mutagenicity tests. In Ames test, Salmonella typhimurium TA98 and TA100 were used to identify mutagenic property, and the number of histidine revertants was measured. In SOS umu test, Salmonella typhimurium TA1535 containing plasmid pSK1002 was used as a test strain, and we monitored the levels of umu operon expression by measuring the $\beta-galactosidase$ activity. Mutagenic activity in any assays we tested was not found. After treating S-9 mixture with GGT, mutagenic activity was also not found. The results of this study suggested that there was no DNA damage and mutagenicity of GGT.

창이자 및 꿀풀하고초에 의한 NAD(P)H:quinone reductase와 glutathione S-transferase의 유도

손윤희,이기택,박신화,조경희,임종국,남경수,Shon, Yun-Hee,Lee, Ki-Taek,Park, Sin-Hwa,Cho, Kyoung-Hee,Lim, Jong-Kook,Nam, Kyung-Soo 한국생약학회 2001 생약학회지 Vol.32 No.4

Ethanol extracts from Xanthii Fructus (XFE) and Prunellae Spica (PSE) were investigated for the effects on the induction of cancer chemoprevention-associated enzymes. The following effects were measured: (a) induction of quinone reductase (QR) (b) induction of glutathione S-transferase (GST) (c) reduced glutathione (GSH) level. XFE and PSE were potent inducers of quinone reductase activity in Hepa1c1c7 murine hepatoma cells. Glutathione levels were increased with XFE and PSE. In addition, glutathione S-transferase activity was increased with XFE. However, GST activity was not increased with PSE. These results suggest that XFE and PSE have chemopreventive potentials by inducing quinone reductase and increasing GSH levels.

In vitro에서의 댑싸리하고초의 유방암예방효소 활성에 미치는 영향

손윤희,김미경,박선동,남경수,Shon, Yun-Hee,Kim, Mee-Kyung,Park, Sun-Dong,Nam, Kyung-Soo 대한동의생리학회 2006 동의생리병리학회지 Vol.20 No.6

The effect of water extract from Thesium chinese Turczaninow (TCTW) on proliferation of human breast cancer cells, nitric oxide production, nitric oxide synthase expression, and ornithine decarboxylase activity was tested. TCTW inhibited the growth of both estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 human breast cancer cells. Lipopolysaccharide-induced nitric oxide (NO) production was significantly reduced by TCTW at the concentrations of 1.0 (p<0.05) and 5.0 mg/ml (p<0.005). Expression of inducible nitric oxide synthase (iNOS) was also suppressed with the treatment of TCTW in Western blot analysis. TCTW inhibited induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate (TPA), a key enzyme of polyamine biosynthesis, which is enhanced in tumor promotion. Therefore, TCTW is worth further investigation with respect to breast cancer chernoprevention or therapy.

Helicobacter pylori에 의한 위세포독성 및 interleukin-8 생성에 미치는 무의 억제효과

손윤희,서정일,박인경,황철원,김철호,남경수,Shon Yun Hee,Suh Jeong Ill,Park In Kyung,Hwang Cher Won,Kim Cheorl Ho,Nam Kyung Soo 한국생명과학회 2005 생명과학회지 Vol.15 No.4

무(한국 품종 및 일본 품종)를 사용하여 H. pylori에 의한 위세포독성 및 IL-8생성에 미치는 영향을 살펴보았다. 그 결과 무는 H. pylori에 의한 위세포독성을 농도의존적으로$(2\~10 mg/ml)$ 억제하였으며 또한 위암세포인 KATO III에서 분비되는 IL-8의 생성을 억제시킴$(5\~10mg/ml)$을 알았다. 이러한 사실은 무가 H. pylori감염에 의한 위점막세포의 손상을 방지할 수 있음을 나타낸다. The efforts of Korean and Japanese radishes on the viability and interleukin (JL)-8 production by Helicobacter pylori were investigated in human gastric epithelial cell. Cell viability was significantly decreased when they were incubated with H. pylori toxin (p <0.05, p<0.01 and p<0.005). Co-incubation with Korean or Japanese radish increased H. pylori toxin-inhibited cell growth in a concentration-dependent manner. The production of IL-8 was greatly increased in H. pylori-infected gastric epithelial cell in concentration- and time-dependent manners. The increased production of IL-8 was significantly inhibited by Korean (p<0.05 and p<0.01) or Japanese (p<0.05) radishes $(5\~10mg/ml)$. These results indicate that Korean and Japanese radishes have protective effects on H. pylori-inhibited cell growth and H. pylori-induced gastric mucosal cell inflammation by suppressing the production of inflammatory cytokine (IL-8) from gastric epithelial cell.

단삼 분획추출물의 암예방 효과

손윤희,조현정,장현욱,손건호,남경수,Shon Yun-Hee,Cho Hyun-Jung,Chang Hyeun-Wook,Son Kun-Ho,Nam Kyung-Soo 한국생명과학회 2006 생명과학회지 Vol.16 No.3

Six fractions of Salvia miltiorrhiza were tested for their chemopreventive potentials using biochemical markers of carcinogenesis such as quinone reductase (QR), glutathione S-transferase (GST) and glutathione (GSH). Seventy percentage of EtOH extract was potent inducer of QR activity in Hepa1c1c7 murine hepatoma cells. GST activity was increased about 1.4-fold with EtOAc extract at concentration of 50 ${\mu}g/ml$. GSH levels were significantly increased with $H_2O$ extract, 70% EtOH extract and water extract at concentration of 50 ${\mu}g/ml$ (p<0.005). From these results, 70% EtOH extract (250 mg/kg) was intragastrically administered to ICR mice for 14 days. QR, GST and GSH levels were significantly increased with the 70% EtOH treatment. These studies suggest that the 70% EtOH extract of S. miltiorrhiza could be considered as a potential agent for cancer chemoprevention. 본 연구는 단삼 분획추출물로부터 in vitro와 in vivo상에서 QR과 GST의 활성 유도와 GSH의 함량변화를 지표로 암예방 효과를 측정하였다. Hepalcla7 세포에 대한 in vitro상에서의 실험결과 QR 활성 유도율은 70% EtOH 추출물 50 ${\mu}g/ml$ 처리군에서 2.5배로 가장 높은 유도율을 나타내었고, GST 활성 측정은 EtOAc추출물 50 ${\mu}g/ml$농도에서 1.4배의 유도율을 나타내었다. GSH 생성변화를 살펴본 결과에서는 $H_2O$추출물, 70% EtOH 추출물 그리고 water layer 추출물 50 ${\mu}g/ml$ 농도에서 높은 생성율을 나타내었다. 이상의 결과에서 QR활성과 GSH 함량변화에서 높은 증가효과를 나타낸 70% EtOH 추출물을 관류법으로 마우스에 투여하여 in vivo 상에서의 QR과 GST의 활성 변화와 GSH 함량을 측정한 결과 QR, GST활성과 GSH함량이 250 mg 투여시 각각 1.7배 및 1.5배의 활성 증가와 1.4배 함량증가를 측정할 수 있었음으로 70% EtOH추출물은 암예방효과가 가장 높은 것으로 생각된다.

사람 위 상피세포의 염증반응에 대한 무의 효과

손윤희,정유선,서정일,박인경,남경수,Shon, Yun-Hee,Chung, Yoo-Sun,Suh, Jeong-Ill,Park, In-Kyung,Nam, Kyung-Soo 한국생명과학회 2006 생명과학회지 Vol.16 No.1

The effects of Korean and Japanese radishes on inflammatory reaction that involves arachidonic acid cascades were investigated in human epithelial gastric cell. The activities of type I (porcine pancreas) and type II (Crotalus atrox) phospholipase $A_2(PLA_2$) were inhibited by radish. Cyclooxygenase-2 (COX-2) activity was significantly suppressed by radish (p<0.05, p<0.01 and p<0.005). The nitric oxide production was also inhibited by radish. The Korean radish was more effective in inhibition of $PLA_2$ and COX-2 activities and nitric oxide production than Japanease radish. These results indicate that radish has a protective effect on gastric epithelial cell inflammation by suppressing the activities of $PLA_2$ and COX-2 activities and nitric oxide production from gastric epithelial cell.

Phase Ⅰ, phase Ⅱ 효소 및 ornithine decarboxylase에 미치는 해양심층수의 영향

손윤희(Yun-Hee Shon),김미경(Mee-Kyung Kim),장정선(Jung-Sun Jang),정은정(Eun-Jung Jung),남경수(Kyung-Soo Nam) 한국생명과학회 2008 생명과학회지 Vol.18 No.3

동해에서 취수한 해양심층수의 암예방 효능을 알아보고자 암발생 억제물질의 생화학적 표식자(biochemical markers)인 CYP 1A2 활성, phase II 효소인 QR과 GST의 활성, GSH 함량 및 ODC 활성에 미치는 영향을 살펴보았다. 해양심층수는 암의 개시단계(initiation)를 유발시키는 것으로 알려진 CYP 1A2 활성을 경도의존적으로 저해시켰다. 해양심층수를 Hepa 1c1c7 세포에 경도별(100∼1,000)로 처리하였을 때 phase II 생체 해독효소인 QR과 GST의 활성은 최대 20%의 증가를 나타내었고, 외부의 독성물질이나 대사산물로부터 세포를 보호하는 역할을 하는 GSH의 함량은 26∼40%의 증가를 나타내었다. 그리고 발암과정의 촉진/진행단계에 관여하는 ODC의 활성은 해양심층수의 경도 800과 1,000에서 20%와 35%의 저해율을 나타내었으며, 경도 1,000을 처리한 군에서는 양성대조군인 DFMO와 같은 저해율을 나타내었다. 그러므로 본 연구 결과에 의하면 동해 해양심층수는 발암과정과 관련된 개시 및 촉진/진행단계를 저해시켜 암예방 효능을 나타낼 것으로 사료된다. Deep sea water was tested for cancer chemopreventive activity by measuring the activities of β- naphthoflavone (β-NF)-induced cytochrome P 450 1A2 (CYP 1A2), quinone reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, and ornithine decarboxylase (ODC) activity. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of 100∼1,000) showed a hardness-dependent inhibition of CYP 1A2 activity. QR and GST activities were induced about 1.1∼1.2 fold with the treatment of deep sea water in murine hepatoma Hepa 1c1c7 cells. In addition GSH levels were increased 1.3∼1.4 fold in a hardness range of 100∼1,000. The deep sea water showed 20.3 and 35.0% inhibition of 12-O- tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity at hardness 800 and 1,000, respectively. Therefore, deep sea water is worth further investigation with respect to cancer chemoprevention or therapy.

해양심층수의 cytochrome P450 1A1, aromatase 및 MMP-9 활성 억제 효과

손윤희(Yun-Hee Shon),김미경(Mee-Kyung Kim),남경수(Kyung-Soo Nam) 한국생명과학회 2008 생명과학회지 Vol.18 No.4

동해 해양심층수의 유방암예방 효능과 전이에 미치는 영향을 알아보기 위해 cytochrome P450 1A1 활성과 aromatase 활성 및 유방암세포의 침윤성, 이와 관련된 MMP-9의 활성과 그 단백질 발현에 미치는 영향을 조사하였다. 해양심층수는 체내외의 여러 화학물질을 체내에서 활성화시켜 발암이나 돌연변이 등을 유발시키는 것으로 알려진 cytochrome P450 1A1을 경도의존적으로 저해시켰다. 또한 호르몬 의존성 유방암의 진행에 관여하는 aromatase의 활성도 경도의존적으로 저해시켰다(5.6∼51.9%). 해양심층수 처리에 의해 사람유방암세포인 MDA-MB-231 세포의 침윤성은 73.7∼29.4%로 감소하였으며, 세포의 침윤시 작용하는 단백질 분해 효소인 MMP-9의 활성과 단백질 발현도 경도의존적으로 억제되었다. 따라서 해양심층수는 유방암 예방과 전이관련의 더 많은 연구에 의해 유방암 예방과 전이 억제작용을 증명할 수 있을 것으로 보인다. Deep sea water from the East sea was tested for breast cancer chemoprevention and metastasis by measuring the activities of cytochrome P450 1A1 and aromatase, invasiveness, and activity and expression of matrix metalloproteinase (MMP)-9 in breast MDA-MB-231 cancer cell. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of 100∼1,000) showed a hardness-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity. Deep sea water showed 27.1, 45.4 and 51.9% inhibition of microsomal aromatase activity at the hardness of 600, 800 and 1,000, respectively. In addition deep sea water inhibited not only the invasiveness of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MDA-MB-231 cells through matrigel-coated membrane in a hardness-dependent manner but also the activity and expression of MMP-9 in MDA-MB-231 cell.

연구논문 : 생명과학 ; 키토산 올리고사카라이드가 다이옥신 처리 마우스에 미치는 영향

손윤희 ( Yun Hee Shon ),박인국 ( In Kook Park ),문일수 ( Il Soo Moon ),장현욱 ( Hyeun Wook Chang ),박인경 ( In Kyung Park ),남경수 ( Kyung Soo Nam ) 영남대학교 약품개발연구소 2003 영남대학교 약품개발연구소 연구업적집 Vol.13 No.-