Ligularia fischeri regulates lung cancer cell proliferation and migration through down-regulation of epidermal growth factor receptor and integrin b1 expression

조영락,김진규,김재현,오좌섭,서동완 한국유전학회 2013 Genes & Genomics Vol.35 No.6

In the present study, we report the effect and molecular mechanism of Ligularia fischeri (LF) on proliferation and migration in human lung cancer cells. LF-mediated inhibition of cell proliferation in p53 wildtype A549 and p53-deficient H1299 cells is accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases and cyclins, resulting in pRb hypophosphorylation and G1 phase cell cycle arrest. In contrast, LF inhibits cell migration in A549 cells, but not in H1299 cells. These regulatory effects of LF on cell proliferation and migration are associated with inactivation of mitogenic signaling pathways such as ERK, Akt and p70S6K, and down-regulation of epidermal growth factor receptor and integrin b1 expression. Collectively, these findings suggest further development and evaluation of LF for the prevention and treatment of lung cancer with mutated p53 as well as wild-type p53.

Radiofrequency Catheter Ablation for Unifocal Premature Ventricular Complexes Triggering Recurrent Ventricular Fibrillations in a Young Man Without Structural Heart Disease

조영락,박종성 대한심장학회 2012 Korean Circulation Journal Vol.42 No.8

A 17-year-old man was referred for aborted sudden cardiac death. Ventricular fibrillation (VF) was recorded by automated external defi-brillator. Post-resuscitation electrocardiograms showed frequent monomorphic premature ventricular complexes (PVCs), with left bundle branch block configuration and inferior axis. Cardiac arrest due to VF recurred twice within the initial 42 hours. Rhythm monitoring re-vealed multiple episodes of sustained VF triggered by a triplet of monomorphic PVCs having similar morphology with isolated PVCs. Com-prehensive cardiologic workup revealed no structural heart disease and ion-channelopathies. With the impression of idiopathic VF trig-gered by unifocal PVCs of right ventricular outflow tract (RVOT) origin, radiofrequency catheter ablation was performed to prevent frequent VF recurrence before implantable cardioverter-defibrillator (ICD) implantation. After successful ablation of the origin of unifocal PVCs at an -terolateral wall of RVOT, the burden of PVCs decreased remarkably and VF did not recur. The patient was discharged after ICD implantation.

Sepiapterin regulates cell proliferation and migration: its association with integrin α3β1 and p53 in human lung cancer cells

조영락,Shin Wook Choi,Dong-Wan Seo 한국유전학회 2011 Genes & Genomics Vol.33 No.5

Tetrahydrobiopterin (BH_4) has been known to be an essential cofactor for nitric oxide synthase as well as the aromatic amino acid hydroxylases, which are involved in regulation of cellular fates including proliferation, migration and differentiation. In the present study, we report that sepiapterin, a stable form of BH_4 precursor, modulates proliferation and migration in human lung cancer cells. Sepiapterin induction of cell proliferation in p53 wild-type A549 cells, but not in p53-deficient H1299 cells, is accompanied by enhanced expression of cell cycle-related proteins such as cyclin-dependent kinase 4(Cdk4), cyclin D and cyclin E, and reduced expression of Cdk inhibitor p21^(WAF1/Cip1), demonstrating that sepiapterin-induced mitogenic responses might be associated with p53 expression status in lung cancer cells. In addition, sepiapterin enhances cell migration in A549 cells, but not H1299 cells. Finally, we show that sepiapterin induces A549 cell proliferation and migration through the activation of Akt and p70^(S6K) signaling pathways, as evidenced by using Akt and p70^(S6K) inhibitor. Collectively, these findings indicate that sepiapterin might play differential roles in regulation of cellular fates, depending on the status of p53 expression in lung cancer. Tetrahydrobiopterin (BH_4) has been known to be an essential cofactor for nitric oxide synthase as well as the aromatic amino acid hydroxylases, which are involved in regulation of cellular fates including proliferation, migration and differentiation. In the present study, we report that sepiapterin, a stable form of BH_4 precursor, modulates proliferation and migration in human lung cancer cells. Sepiapterin induction of cell proliferation in p53 wild-type A549 cells, but not in p53-deficient H1299 cells, is accompanied by enhanced expression of cell cycle-related proteins such as cyclin-dependent kinase 4(Cdk4), cyclin D and cyclin E, and reduced expression of Cdk inhibitor p21^(WAF1/Cip1), demonstrating that sepiapterin-induced mitogenic responses might be associated with p53 expression status in lung cancer cells. In addition, sepiapterin enhances cell migration in A549 cells, but not H1299 cells. Finally, we show that sepiapterin induces A549 cell proliferation and migration through the activation of Akt and p70^(S6K) signaling pathways, as evidenced by using Akt and p70^(S6K) inhibitor.

3 weeks repeated-dose toxicity study on Ligularia fischeri extract

조영락,고혜진,박영진,이재연,박주형,안은경,오좌섭 한국실험동물학회 2015 한국실험동물학회 학술발표대회 논문집 Vol.2015 No.2

산지별 더덕 추출물의 폐암 및 난소암에 대한 항암 효능

조영락 ( Young Rak Cho ),김수현 ( Soo Hyeon Kim ),윤현재 ( Hyun Jae Yoon ),홍삼열 ( Sam Yeol Hong ),고희영 ( Hee Young Ko ),박은희 ( Eun Hee Park ),김명동 ( Myoung Dong Kim ),서동완 ( Dong Wan Seo ) 한국산업식품공학회 2011 산업 식품공학 Vol.15 No.1

Codonopsis lanceolata L. (Campanulaceae) has long been used in traditional Korean medicine to treat bronchitis, cough, and inflammatory diseases, however, the efficacy of anti-tumor activities remains to be defined. In this study the effects of Codonopsis lanceolata (C. lanceolata) on proliferation, migration and adhesion in lung (A549, H1299) and ovarian cancer (SKOV-3) cells were investigated. To assess and compare the pharmacological effects and production places of C. lanceolata, the ethanolic extracts of C. lanceolata from different places in Korea (Hongseong, Yecheon, Yeongwol, Yanggu, Gangjin, and Hoengseong) were prepared. The extract from Hoengseong county did have only marginal anti-proliferative activity in all the cell lines tested, however, other extracts had little or no effect on cell proliferation. The extracts from Hongseong, Gangjin or Hoengseong county had partial anti-migratory activity in lung cancer cells, but not in ovarian cancer cells. In addition, the extract from Hoengseong county had partial anti-adhesive activity in ovarian cancer cells, however, other extracts did not affect cell adhesion in both lung and ovarian cancer cells. Taken together, these findings provide the first description of anti-tumor efficacy of C. lanceolata from different production places in Korea, and suggest that C. lanceolata from Hoengseong county may have therapeutic potential in lung and ovarian cancers.

산지별 더덕 추출물의 폐암 및 난소암에 대한 항암 효능

조영락,김수현,윤현재,홍삼열,고희영,박은희,김명동,서동완 한국산업식품공학회 2011 산업 식품공학 Vol.15 No.1

Codonopsis lanceolata L. (Campanulaceae) has long been used in traditional Korean medicine to treat bronchitis, cough, and inflammatory diseases, however, the efficacy of anti-tumor activities remains to be defined. In this study the effects of Codonopsis lanceolata (C. lanceolata) on proliferation, migration and adhesion in lung (A549, H1299) and ovarian cancer (SKOV-3) cells were investigated. To assess and compare the pharmacological effects and production places of C. lanceolata, the ethanolic extracts of C. lanceolata from different places in Korea (Hongseong, Yecheon, Yeongwol, Yanggu, Gangjin, and Hoengseong) were prepared. The extract from Hoengseong county did have only marginal anti-proliferative activity in all the cell lines tested, however, other extracts had little or no effect on cell proliferation. The extracts from Hongseong, Gangjin or Hoengseong county had partial anti-migratory activity in lung cancer cells, but not in ovarian cancer cells. In addition, the extract from Hoengseong county had partial anti-adhesive activity in ovarian cancer cells, however, other extracts did not affect cell adhesion in both lung and ovarian cancer cells. Taken together, these findings provide the first description of anti-tumor efficacy of C. lanceolata from different production places in Korea, and suggest that C. lanceolata from Hoengseong county may have therapeutic potential in lung and ovarian cancers.

ICR 마우스에서 핑크왐피 추출물의 3주간 반복 투여 독성 연구

박주형,조영락,김영민,강재신,오좌섭,안은경 한국응용생명화학회 2019 Journal of Applied Biological Chemistry (J. Appl. Vol.62 No.2

Medicinal herb in Asian countries has been traditionally used for a long time. However, the safety and adverse effect of medicinal herb have not been established yet. The aim of this study is to evaluate toxicity in the oral administration of Clausena excavata (C. excavata) in male ICR mice for 3 weeks and the noobserved adverse effect level (NOAEL). C. excavata has been used as a medicinal herb for the treatment of dermatopathy, malaria, abdominal pain, dysentery, and enteritis. C. excavata was orally administered daily for 21 days at a dose of 100, 250, 500, 1000, and 2000 mg/kg/day (MPK). There were no significant differences in mortalities, clinical signs, body weight changes, hematological, and serum biochemistry examination in all animals administrated with C. excavate. Consequently, these findings indicated that C. excavata did not affect the toxic effect in ICR mice and the NOAEL of C. excavata was considered as more than 2000 MPK. 핑크왐피는 피부병, 말라리아, 복통, 이질 및 장염 치료를 위한약용 식물로 사용되고 있다. 본 연구의 목적은 핑크왐피의 안전성을 확인하기 위하여, 수컷 ICR 마우스를 이용하여 핑크왐피를 3주 반복 경구 투여하여 최대무독성용량을 평가했다. 핑크왐피를 100, 250, 500, 1000, 및 2000 mg/kg으로 투여한 결과, 모든 시험물질 투여군에서 이상이 관찰되지 않았다. 사망률, 임상 증상, 체중 변화, 혈액 학적 검사 및 혈청 생화학 검사에서 유의적인 차이는 없었고, 경미한 변동은 핑크왐피의 투여로인한 영향이 아닌 정상 범위 내에서의 변화로 간주 되어진다. 결과적으로, 핑크왐피는 모든 시험물질 투여군에서 독성 영향을미치지 않았으며, 핑크왐피의 최대무독성용량은 2000 mg/kg 이상으로 간주되었다.

Effect of ethanol extract from Ligularia fischeri on hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet

박주형,조영락,안은경,오좌섭 한국실험동물학회 2016 한국실험동물학회 학술발표대회 논문집 Vol.2016 No.2

Phytochemical Linarin Enriched in the Flower of Chrysanthemum indicum Inhibits Proliferation of A549 Human Alveolar Basal Epithelial Cells Through Suppression of the Akt-Dependent Signaling Pathway

서동완,조영락,김우기,엄석현 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.12

In this study, we report the anti-proliferative effect and molecular mechanism of Chrysanthemum indicum (C. indicum) on A549 human alveolar basal epithelial cells. We also analyzed the changes in C. indicum component profiles due to modifications of predrying process, flower size, and extraction method. Among the varieties of modifications tested, high-temperature heat dry (HTD) of small flower biotype followed by the methanolic extraction resulted in the strongest antiproliferative activity of C. indicum extract in A549 cells. High-performance liquid chromatography of C. indicum revealed that the levels of acacetin 7-O-rutinoside (linarin) are markedly increased by heat treatment, especially HTD. Finally, we showed that linarin-mediated inhibition of cell proliferation is associated with suppression of Akt activation and induction of cyclin-dependent kinase inhibitor p27Kip1 as evidenced by cell cycle analysis and treatment with LY294002, an inhibitor of phosphatidylinositol 3-kinase/Akt pathway. Taken together, these findings suggest the need for further development and evaluation of linarin from C. indicum for the treatment and prevention of lung cancer.

ICR 마우스에서 청가시덩굴 추출물의 4주간 반복 투여 독성시험

이정아,황민희,조영락,안은경 한국응용생명화학회 2022 Journal of Applied Biological Chemistry (J. Appl. Vol.65 No.4

청가시덩굴은 청미래덩굴속에 속하며 청미래덩굴속 식물들은 전세계적으로 열대 및 아열대 지역에 서식하며 전통 의학에서 오랫동안 사용되어 왔다. 본 연구의 목적은 수컷과 암컷 ICR 마우스를 이용하여 청가시덩굴의 안전성을 확인하기 위해 청가시덩굴 추출물을 4주 동안 경구 투여하여 최대무독성용량을 평가하였다. 청가시덩굴 추출물을 500, 1000 및 2000 MPK 용량으로 4주 동안 매일 경구 투여한 결과 투여한 모든군에서 사망률, 임상 증상, 체중 변화, 섭취량, 혈액학적 분석, 혈청 생화학 검사 및 상대 장기 중량에 유의한 차이가 없었다. 본 연구에서 청가시덩굴 추출물은 ICR 마우스에서 어떠한 독성 효과도 나타내지 않았으며 청가시덩굴 추출물의 최대무독성용량은 2000 MPK 이상으로 간주되었음을 시사한다.