nhibition of Vascular Network Formation on Human Microvessel Endothelial Cell by Betaine

Eui-Yeun Yi,Yung-Jin Kim 대한암예방학회 2008 Journal of cancer prevention Vol.13 No.4

Angiogenesis, the sprouting and remodeling of capillaries, plays a central role in a variety of physiologic and pathologic processes. Anti-angiogenesis therapy has recently been found to be one of the most promising new anti-cancer therapeutic strategies. Natural products comprise a major source of small molecular weight angiogenesis inhibitors. Angiogenesis and inflammation often share common pathways, and these two biological processes are also closely coupled with cancer. Both angiogenesis and inflammation are exacerbated by increased production of cytokines, growth factors and proteolytic enzymes. Betaine has been shown to have anti-inflammatory effects. In this study, we investigated the possibility that betaine inhibit angiogenesis. Therefore, we examined the effect of betaine on the vascular network formation of HMEC-1. Although betaine does not show any effect on the viability of HMEC-1, the treatment of betaine inhibited the tube formation of human microvessel endothelial cells (HMEC-1). This result suggests that betaine act for an angiogenic inhibitor.

A Novel Anti-cancer Agent, SJ-8029, Inhibits Angiogenesis and Induces Apoptosis

Yi Eui-Yeun,Jeong Eun-Joo,Song Hyun-Seok,Kang Dong-Wook,Joo Jeong-Ho,Kwon Ho-Seok,Lee Sun-Hwan,Park Si-Kyung,Chung Sun-Gan,Cho Eui-Hwan,Kim Yung-Jin The Korean Society for Biomedical Laboratory Scien 2006 Journal of biomedical laboratory sciences Vol.12 No.3

A new piperazine derivative, 8J-8029, is a synthetic anti-cancer agent which exhibits both microtubule and topoisomerase II inhibiting activities. In this study, we investigated the ability of 8J-8029 for anti-angiogenesis and apoptosis. 8J-8029 decreased the bFGF-induced angiogenesis in the CAM and the mouse Matrigel implants, in vivo. 8J-8029 inhibited the proliferation, migration, invasion, tube fonnation, and expression of MMP-2 in BAECs. In addition, 8J-8029 reduced the cell viability in HepG2 cells, caused the production of fragmented DNA and the morphological changes corresponding to apoptosis. 8J-8029 also elicited the release of cytochrome c and the activation of caspase-3. Taken together, these results suggest 8J-8029 may be a candidate for anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.

Xylitol inhibits in vitro and in vivo angiogenesis by suppressing the NF-κB and Akt signaling pathways

YI, EUI-YEUN,KIM, YUNG-JIN Spandidos Publications 2013 International journal of oncology Vol.43 No.1

<P>Angiogenesis is an important process involved in tumor growth and metastasis. Many studies have investigated the use of natural compounds such as angiogenic inhibitors. Xylitol is a 5-carbon sugar alcohol and is an artificial sweetener that has been used in chewing gums to prevent tooth decay. Xylitol has been also known to inhibit inflammatory cytokine expression induced by lipopolysaccharide (LPS). Since angiogenesis and inflammation share a common signaling pathway, we investigated the role of xylitol in angiogenesis. Xylitol inhibited the migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs). Xylitol also inhibited in vivo angiogenesis in a mouse Matrigel plug assay. Furthermore, mRNA expression of vascular endothelial growth factor (VEGF), VEGFR-II (KDR), basic fibroblast growth factor (bFGF), bFGFR-II, matrix metalloproteinase-2 (MMP-2) and MMP-9 of HUVECs decreased following treatment with xylitol. These anti-angiogenic effects of xylitol are exerted through inhibition of NF-κB and Akt activation. Taken together, these results suggest that xylitol acts as a beneficial angiogenesis inhibitor.</P>

Betaine inhibits in?vitro and in?vivo angiogenesis through suppression of the NF-κB and Akt signaling pathways.

Yi, Eui-Yeun,Kim, Yung-Jin Lychnia 2012 International journal of oncology Vol.41 No.5

<P>Angiogenesis is defined as the formation of new blood vessels form existing vessels surrounding a tumor. The process of angiogenesis is an important step for tumor growth and metastasis, as is inflammation. Thus, angiogenesis inhibitors that suppress inflammation have been studied as an anticancer treatment. Recently, many research groups have investigated the anti-angiogenic activity of natural compounds since some have been demonstrated to have anticancer properties. Among many natural compounds, we focused on betaine, which is known to suppress inflammation. Betaine, trimethylglycine (TMG), was first discovered in the juice of sugar beets and was later shown to be present in wheat, shellfish and spinach. In Southeast Asia, betaine is used in traditional oriental medicine for the treatment of hepatic disorders. Here, we report the anti-angiogenic action of betaine. Betaine inhibited in?vitro angiogenic cascade, tube formation, migration and invasion of human umbilical vein endothelial cells (HUVECs). Betaine also inhibited in?vivo angiogenesis in the mouse Matrigel plug assay. The mRNA expression levels of basic fibroblast growth factor (bFGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in HUVECs were decreased by betaine treatment. In addition, betaine suppressed NF-κB and Akt activation.</P>

Anti-angiogenic activity of KR-31482, a new benzopyran derivative

Yi, Eui Yeun,Kang, Jung A,Song, Hyun Seok,Yi, Hkyu Yang,Yoo, Sung En,김영진 대한암예방학회 2006 Journal of cancer prevention Vol.11 No.3

Extract of Balloon-flower Inhibited In Vitro Angiogenesis in Human Umbilical Vein Endothelial Cells

Eui-Yeun Yi(이의연),Yung-Jin Kim(김영진) 한국생명과학회 2017 생명과학회지 Vol.27 No.9

혈관신생과정은 종양 형성과 이동에 필수적인 과정으로 촉진제와 저해제에 의하여 조절되며, 이러한 혈관신생과정의 저해는 새로운 항암치료 기법으로 이용하고 있다. 최근, 한약재와 식료품으로부터 추출한 천연물을 새로운 치료 물질로 널리 이용하고 있으며, 실제 in vitro 뿐만 아니라 in vivo 상에서도 항암 효과가 나타나는 것을 확인하였다. 그 중 도라지는 아시아에서 한약재와 식료품으로 오랫동안 사용 되어왔다. 본 연구에서는 도라지 추출물이 in vitro 상에서 인간 제대 정맥 내피 세포의 혈관신생을 억제하는 효과에 대해 조사하였다. 도라지 추출물은 세포독성 없이, 혈관 형성 및 이동, 침윤 현상을 모두 억제하는 효과를 보였다. 특히, 세포 이동은 80% 정도 감소 시켰으며 침윤 현상이 거의 나타나지 않는 것을 확인하였다. 이러한 결과를 토대로 도라지 추출물은 혈관신생 억제제로 이용할 수 있으며, 더 나아가 항암제로 개발될 수 있을 것이라 사료된다. Angiogenesis is an essential step in tumoral growth and metastasis and is regulated by a balance between stimulators and inhibitors. Recently, antiangiogenic target therapy has shown promise as a new type of chemotherapy. Natural products have attracted widespread attention worldwide as a useful source of novel therapeutic compounds. The balloon-flower has long been used as a traditional medicinal material and food in Asia. In this study, we investigated whether extract of balloon-flower would inhibit in vitro angiogenesis and vascular-like network formation in human umbilical vein endothelial cells (HUVECs). The extract of Balloon-flower did not affect the viability of HUVECs. However, treatment with the Balloon-flower extract suppressed tube formation of HUVECs. In addition, after treatment with the Balloon-flower extract, cell migration decreased about 80%, and cell invasion was almost completely inhibited. Taken together, these results suggest that extract of Balloon-flower may have potential as an angiogenic inhibitor and that it could be developed as an anticancer agent.

Mitochondrial dysfunction suppresses p53 expression via calcium-mediated nuclear factor-kB signaling in HCT116 human colorectal carcinoma cells

( Young-kyoung Lee ),( Eui-yeun Yi ),( Shi-young Park ),( Won-jun Jang ),( Yu-seon Han ),( Myeong-eun Jegal ),( Yung-jin Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.6

Mitochondrial DNA (mtDNA) mutations are often observed in various cancer types. Although the correlation between mitochondrial dysfunction and cancer malignancy has been demonstrated by several studies, further research is required to elucidate the molecular mechanisms underlying accelerated tumor development and progression due to mitochondrial mutations. We generated an mtDNA-depleted cell line, ρ⁰, via long-term ethidium bromide treatment to define the molecular mechanisms of tumor malignancy induced by mitochondrial dysfunction. Mitochondrial dysfunction in ρ⁰ cells reduced drug-induced cell death and decreased the expression of pro-apoptotic proteins including p53. The p53 expression was reduced by activation of nuclear factor-κB that depended on elevated levels of free calcium in HCT116/ρ⁰ cells. Overall, these data provide a novel mechanism for tumor development and drug resistance due to mitochondrial dysfunction. [BMB Reports 2018; 51(6): 296-301]

Melatonin suppresses tumor angiogenesis by inhibiting HIF-1&agr; stabilization under hypoxia

Park, Shi-Young,Jang, Won-Jun,Yi, Eui-Yeun,Jang, Ji-Yeong,Jung, Yunjin,Jeong, Joo-Won,Kim, Yung-Jin Blackwell Publishing Ltd 2010 Journal of pineal research Vol.48 No.2

<P>Abstract: </P><P>Angiogenesis is an important mediator of tumor progression. As tumors expand, diffusion distances from the existing vascular supply increases, resulting in hypoxia in the cancer cells. Sustained expansion of a tumor mass requires new blood vessel formation to provide rapidly proliferating tumor cells with an adequate supply of oxygen and nutrients. The key regulator of hypoxia-induced angiogenesis is the transcription factor known as hypoxia-inducible factor (HIF)-1. HIF-1&agr; is stabilized by hypoxia-induced reactive oxygen species (ROS) and enhances the expression of several types of hypoxic genes, including that of the angiogenic activator known as vascular endothelial cell growth factor (VEGF). In this study, we found that melatonin, a small lipophilic molecule secreted primarily by the pineal gland, destabilizes hypoxia-induced HIF-1&agr; protein levels in the HCT116 human colon cancer cell line. This destabilization of HIF-1&agr; resulted from the antioxidant activity of melatonin against ROS induced by hypoxia. Moreover, under hypoxia, melatonin suppressed HIF-1 transcriptional activity, leading to a decrease in VEGF expression. Melatonin also blocked in vitro tube formation and invasion and migration of human umbilical vein endothelial cells induced by hypoxia-stimulated conditioned media of HCT116 cells. These findings suggest that melatonin could play a pivotal role in tumor suppression via inhibition of HIF-1-mediated angiogenesis.</P>

Aging and Cancer : Melatonin inhibits hypoxia-induced tumor angiogenesis

( Shi Young Park ),( Ji Yeong Jang ),( Eui Yeun Yi ),( Won Jun Jang ),( Kook Hee Ahn ),( Joo Won Jeong ),( Yung Jin Kim ) 한국생화학분자생물학회 (구 한국생화학회) 2008 생화학분자생물학회 춘계학술발표논문집 Vol.2008 No.-

간경변증 환자에서 고암모니아혈증과 Helicobacter pylori의 연관성

김영수,최원,신현주,신용운,권계숙,이돈행,김범수,조현근,이재수,홍의수,박은재 대한소화기학회 1999 대한소화기학회지 Vol.34 No.3

Background/Aims: We examined the correlation between hyperammonemia and gastric Helicobacter pylori (H. pylori) infection in patients with liver cirrhosis. Methods: We studied 31 patients with liver cirrhosis and 34 normal controls. However, the cirrhotic group did not include patients who had a bleeding tendency or hepatic encephalopathy. We performed gastroscopy, obtained gastric juice (3-4 mL) and antral biopsy specimens, and examined the ammonia levels of blood and gastric juice in each group. Results: In the cirrhotic group, there was no difference in blood ammonia levels between the H. pylori- positive (HP+) and negative (HP-) groups. However, the ammonia levels of gastric juice in the HP+ group showed a tendency to be higher than those in the HP- group (p=0.0773). Child-Pugh scores in the HP+ group were significantly lower than those in the HPQ group (p= 0.0309). By multiple regression analysis, factors affecting the ammonia levels of blood were determined. They were age (coefficient 1.2462, p=0.0256) in the control group (r2=0.2821), and ammonia levels of gastric juice (coefficient 0.007417, p=0.0322) in the cirrhotic group (r2=0.3127). On the other hand, Child- Pugh scores (coefficient 12.508122, p=0.0883) indicated a slight correlation with the blood ammonia levels in the cirrhotic group. Conclusions: It seems that gastric H. pylori infection is associated with hyperammonia in patients with liver cirrhosis.