• 동국한의학연구소논문집
• /
• 제7권1호
• /
• pp.43-51
• /
• 1998

본 실험은 김 추출물이 고콜레스테롤증 유발시 발생되는 신장내의 과도한 콜레스테롤 축적에 대한 감소효과의 조사를 위해 ICR 생쥐에 Triton WR-1339(TX) 복강주사로 인위적인 고지혈증을 유발시킨 후 김 추출물(30mg/kg)을 복강주사하여 시간의 경과에 따른 신장조직에서의 콜레스테롤을 비롯한 지방입자의 축적양상 변화를 관찰하였다. TX 주사로 고콜레스테롤증 유발시 신장조직 전지역, 즉 사구체, 근위곱슬세관, 원위곱슬세관 그리고 헨레고리에서 콜레스테롤을 비롯한 지방입자의 축적이 증가되는 것으로 나타났다. 그러나 고콜레스테롤증시 나타나는 신장내의 일련의 변화는 김 추출물 처리후 콜레스테롤을 비롯한 지방입자의 축적이 신장조직 전 지역에서 현저하게 감소된 것으로 관찰되었으며, 이러한 감소는 TX 주사후 48시간에서 가장 잘 나타났다. 이상의 결과로 볼 때 해조류 김 추출물은 고콜레스증 유발된 신장내의 과도한 콜레스테롤을 비롯한 지방축적을 감소시키는 항고콜레스테롤증 효과을 하는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제17권3호
• /
• pp.203-208
• /
• 2013

As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced $[^3H]$-thymidine incorporation, cell cycle progression from $G_0/G_1$ to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptor${\beta}$(PDGF-$R{\beta}$) enhanced by PDGF at $Tyr^{579}$, $Tyr^{716}$, $Tyr^{751}$, and $Tyr^{1021}$ residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and $PLC{\gamma}1$. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-$R{\beta}$ autophosphorylation, and subsequently PDGF-$R{\beta}$-mediated downstream signaling pathways.

• 한국잡초학회지
• /
• 제2권1호
• /
• pp.41-46
• /
• 1982

다년생잡초(多年生雜草)인 올미와 올방개에 대한 초(初), 중(中), 후기(後期) 처리약제(處理藥劑)의 작용성(作用性)을 밝혀 방제체계(防除體系)의 기초자료(基礎資料)를 얻고저 본시험(本試驗)을 실시(實施)하였든 바 그 결과(結果)를 요약(要約)하면 다음과 같다. 1. 올미에 대한 살초작용(殺草作用)을 보면 초기처리약제(初期處理藥劑)로서 유효(有效)한 제초제(除草劑)는 지상하부(地上下部)가 완전살초(完全殺草)로 재생(再生)하지 않는 SW-751 제초제(除草劑)와 지상부(地上部) 고사(枯死)되고, 일정기간(一定期間) 억제(抑制)되었다가 재생(再生)하는 Chloromethoxynil, CNP, Oxadiazon 약제(藥劑)로서 억초기간(抑草期間)은 14~24일간(日間)이었다. 2. 중기처리약제(中期處理藥劑)로서는 속효적(速効的) 살초반응(殺草反應)을 보인 약제(藥劑)는 ACN로서 억초기간(抑草期間)은 28~31일간(日間)이었으나 재생(再生)되었으며 재생부위(再生部位)는 측아(側芽)에서 출아(出芽)하는 것으로 사료(思料)되었다. 3. 살초효과(殺草效果)가 있는 제초제(除草劑)는 괴경(塊莖) 식부심도(植付深度)가 깊은 것이 억초기간(抑草期間)이 길었다. 4. 올미의 살초효과(殺草效果)를 류재별(類在別)로 나누어 보면 SW-751과 같이 완전살초(完全殺草)로 재생(再生)되지 않는 형(型)과 ACN 및 diphenylether 계(系)인 Chloromethoxynil, CNP와 같이 지상부(地上部)가 고사(枯死)한 후(後) 일정기간(一定期間)(억초기간(抑草期間)) 지난 후(後) 재생(再生)하는 형(型), Molinate, Benthiocarb, Butachlor 등과 같이 살초작용(殺草作用)이 없는 형(型)으로 나눌 수 있었다. 5. 올방개에 대한 살초작용(殺草作用)을 보면 초기처리약제(初期處理藥劑)로서 유효(有效)한 제초제(除草劑)는 Chloromethoxynil, CNP, Oxadiazon, SW-751로서 억초기간(抑草期間)은 13~25일(日)이었다. 6. 올방개의 중기처리약제(中期處理藥劑)로서는 Chloromethoxynil, SST-5, TH63, 12~14이었다. 7. 올방개의 후기처리제(後期處理劑)는 Bentazon, 2, 4-D(sodium) 및 MCP(sodium) 등 hormone 계(系)와 Bentazon과 hormone계(系)의 혼합제(混合劑)인 Glaszin D 또는 Glaszin M가 억초작용(抑草作用)도 강하고 억초기간(抑草期間)도 길었다. 8. 이상 올미, 올방개에 대한 억제체계면(抑制體系面)에서 보면 초기처리(初期處理)로서 Chloromethoxynil, CNP, SW-751를 처리(處理)하여 일년생(一年生) 및 다년생잡초방제(多年生雜草防除)를 용이(容易)하게 하는 한편, 다년생(多年生)의 재생(再生)되는 잡초방제(雜草防除)를 위하여는 Glaszin D를 사용(使用)하는 것이 방제효과(防除效果)를 높일 수 있는 방법(方法)이 될 수 있었다.

• 한국생물물리학회:학술대회논문집
• /
• 한국생물물리학회 2003년도 정기총회 및 학술발표회
• /
• pp.80-80
• /
• 2003

${\beta}$-lapachone(${\beta}$-Lap), a natural o-naphthoquinone, presents in the bark of the Lapacho tree. ${\beta}$-Lap is cytotoxic against a variety of human cancer cells and it potentiates the anti-tumor effect of Taxol. In addition, ${\beta}$-Lap has been reported to radiosensitize cancer cells by inhibiting the repair of radiation-induced DNA damage.In the present study, we investigated the cytotoxicity of ${\beta}$-Lap against RKO human colorectal cancer cells as well as the combined effect of ${\beta}$-LaP and ionizing radiation. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h killed almost 90％ of the clonogenic cells. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h or longer also caused massive apoptosis. Unlike other cytotoxic agents, ${\beta}$-Lap did not increase the expression of p53 and p21 and it suppressed the NFkB expression. The expression of Caspase 9 and 3 was minimally altered by ${\beta}$-Lap. Radiation and ${\beta}$-Lap acted synergistically in inducing clonogenic cell death and apoptosis in RKO cells when ${\beta}$-Lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5 ${\mu}$M of ${\beta}$-Lap starting 5 h after irradiation was as effective as that starting immediately after irradiation. The mechanisms of ${\beta}$-Lap-induced cell killing is controversial but a recent hypothesis is that ${\beta}$-Lap is activated by NAD(P)H: quinone-onidoreductase (NQO1) in the cells followed by an elevation of cytosolic Ca$\^$2+/ level and activation of proteases leading to apoptosis. It has been reported that NQO1 level in cells is markedly up-regulated for longer than 10 h after irradiation. Indeed, using immunological staining of NQO1, we observed a significant elevation of NQO1 expression in RKO cells 5h after 2-4 Gy irradiation. Such a prolonged elevation of NQO1 level after irradiation may be the reasons why the ${\beta}$-Lap treatment applied S h after irradiation was as effective as that applied immediately after irradiation in killing the cells. In view of the fact that the repair of radiation-induced damage is usually completed within 1-2 h after irradiation, it is highly likely that the ${\beta}$-Lap treahment applied 5 h after irradiation could not inhibit the repair of radiation-induced damage. For in vivo study, RKO cells were injected S.C. into the hind-leg of Nu/Nu mice, and allowed to grow to 130 mm3 tumor. The mice were i.p. injected with ${\beta}$-lapachone or saline 2 h after irradiation of tumors with 10 Gy of X-rays. The radiation induced growth delay was increased by 2.4 $\mu\textrm{g}$/g of ${\beta}$-lapachone. Taken together, we may conclude that the synergistic interaction of radiation and ${\beta}$-Lap in killing cancer cells is not due to radiosensitization by ${\beta}$-Lap but to an enhancement of ${\beta}$-Lap cytotoxicity by radiation through an upregulation of NQO1. The fact that NQO1 is elevated in tumors and that radiation causes prolonged increase of the NQO1 expression may be exploited to preferentially kill tumor cells using ${\beta}$-Lap in combination with radiotherapy.